|
|
| leukotriene B4 |
|
| CHEBI:15647 |
|
| leukotriene B4 |
|
| A leukotriene composed of (6Z,8E,10E,14Z)-icosatetraenoic acid having (5S)- and (12R)-hydroxy substituents. It is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. |
|
This entity has been manually annotated by the ChEBI Team.
|
|
|
CHEBI:6421, CHEBI:10933, CHEBI:25024
|
|
| ChemicalBook:CB7159905, eMolecules:539941, ZINC000004623738 |
|
|
Molfile
XML
SDF
|
|
|
more structures >>
|
|
call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__175769125677565__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__175769125677565__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:15647","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__175769125677565__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"175769125677565","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__175769125677565__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol LTB - Ideal conformer Mrv1927 06102109593D starting HoverWatcher_5 Time for openFile(LTB - Ideal conformer Mrv1927 06102109593D 56 55 0 0 0 0 999 V2000 5.5700 -2.5910 -2.1440 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5490 -3.1440 -1.0700 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8210 -4.4550 -0.9850 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2220 -2.3600 0.1750 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9600 -0.8990 -0.1960 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6280 -0.1030 1.0670 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3670 1.3580 0.6960 C 0 0 2 0 0 0 0 0 0 0 0 0 5.5670 1.9420 0.1860 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9210 2.1150 1.9210 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6900 2.6240 1.9780 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7280 2.3360 0.9120 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4550 2.7690 1.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5070 2.4800 -0.0490 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7650 2.9080 0.0550 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7550 2.6110 -1.0420 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.4210 -4.5200 2.2930 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2530 3.8380 -1.5790 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8310 -3.4850 1.2440 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5970 -2.7020 0.7900 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.0070 -1.6670 -0.2590 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7730 -0.8840 -0.7130 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1770 0.1350 -1.7460 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8450 1.3930 -1.5900 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9180 1.7950 -0.4720 C 0 0 1 0 0 0 0 0 0 0 0 0 6.0290 -4.9150 -1.8100 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3330 -2.7800 0.6460 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0610 -2.4140 0.8690 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8490 -0.4790 -0.6670 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1220 -0.8450 -0.8900 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7400 -0.5230 1.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4670 -0.1570 1.7620 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5880 1.4060 -0.0640 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2820 2.0030 0.8350 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5990 2.2460 2.7510 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4030 3.2490 2.8100 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0380 1.7760 0.0420 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1450 3.3280 1.8870 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1970 1.9200 -0.9190 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0750 3.4670 0.9250 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2640 2.0410 -1.8300 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7040 4.3970 -0.9320 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5290 0.9010 0.0160 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4640 2.3980 0.2540 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2350 2.1420 -2.2630 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7400 -0.1710 -2.6160 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3290 -0.3770 0.1440 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0450 -1.5710 -1.1450 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4500 -2.1740 -1.1160 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7340 -0.9800 0.1730 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6930 -5.2070 1.8610 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9770 -4.0130 3.1500 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3000 -5.0780 2.6160 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1530 -2.1950 1.6470 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8690 -3.3890 0.3580 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2740 -3.9920 0.3870 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5580 -2.7980 1.6760 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 0 0 0 2 3 1 0 0 0 0 2 4 1 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 7 9 1 0 0 0 0 9 10 2 0 0 0 0 10 11 1 0 0 0 0 11 12 2 0 0 0 0 12 13 1 0 0 0 0 13 14 2 0 0 0 0 14 15 1 0 0 0 0 15 17 1 0 0 0 0 15 24 1 0 0 0 0 24 23 1 0 0 0 0 23 22 2 0 0 0 0 22 21 1 0 0 0 0 21 20 1 0 0 0 0 20 19 1 0 0 0 0 19 18 1 0 0 0 0 18 16 1 0 0 0 0 3 25 1 0 0 0 0 4 26 1 0 0 0 0 4 27 1 0 0 0 0 5 28 1 0 0 0 0 5 29 1 0 0 0 0 6 30 1 0 0 0 0 6 31 1 0 0 0 0 7 32 1 6 0 0 0 8 33 1 0 0 0 0 9 34 1 0 0 0 0 10 35 1 0 0 0 0 11 36 1 0 0 0 0 12 37 1 0 0 0 0 13 38 1 0 0 0 0 14 39 1 0 0 0 0 15 40 1 6 0 0 0 17 41 1 0 0 0 0 24 42 1 0 0 0 0 24 43 1 0 0 0 0 23 44 1 0 0 0 0 22 45 1 0 0 0 0 21 46 1 0 0 0 0 21 47 1 0 0 0 0 20 48 1 0 0 0 0 20 49 1 0 0 0 0 19 53 1 0 0 0 0 19 54 1 0 0 0 0 18 55 1 0 0 0 0 18 56 1 0 0 0 0 16 50 1 0 0 0 0 16 51 1 0 0 0 0 16 52 1 0 0 0 0 M END): 19 ms reading 56 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 56 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
|
| Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice. |
|
Read full article at Wikipedia
|
InChI=1S/C20H32O4/c1- 2-3-4-5-6-9-13-18(21)14-10-7-8-11-15-19(22)16-12-17-20(23)24/h6-11,14-15,18-19,21-22H,2-5,12-13,16-17H2,1H3,(H,23,24)/b8-7+,9-6-,14-10+,15-11-/t18-,19-/m1/s1 |
| VNYSSYRCGWBHLG-AMOLWHMGSA-N |
| CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O |
|
|
Mus musculus
(NCBI:txid10090)
|
Source: BioModels - MODEL1507180067
See:
PubMed
|
|
Phaseolus vulgaris
(NCBI:txid3885)
|
See:
DOI
|
|
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
|
|
|
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
|
|
|
vasoconstrictor agent
Drug used to cause constriction of the blood vessels.
|
|
View more via ChEBI Ontology
|
Outgoing
|
leukotriene B4
(CHEBI:15647)
has functional parent
icosa-6,8,10,14-tetraenoic acid
(CHEBI:36045)
leukotriene B4
(CHEBI:15647)
has role
human metabolite
(CHEBI:77746)
leukotriene B4
(CHEBI:15647)
has role
mouse metabolite
(CHEBI:75771)
leukotriene B4
(CHEBI:15647)
has role
plant metabolite
(CHEBI:76924)
leukotriene B4
(CHEBI:15647)
has role
vasoconstrictor agent
(CHEBI:50514)
leukotriene B4
(CHEBI:15647)
is a
dihydroxy monocarboxylic acid
(CHEBI:35972)
leukotriene B4
(CHEBI:15647)
is a
hydroxy polyunsaturated fatty acid
(CHEBI:140345)
leukotriene B4
(CHEBI:15647)
is a
leukotriene
(CHEBI:25029)
leukotriene B4
(CHEBI:15647)
is a
long-chain fatty acid
(CHEBI:15904)
leukotriene B4
(CHEBI:15647)
is conjugate acid of
leukotriene B4(1−)
(CHEBI:57461)
|
|
|
Incoming
|
10,11-dihydro-12-oxoleukotriene B4
(CHEBI:134417)
has functional parent
leukotriene B4
(CHEBI:15647)
10,11-dihydro-20,20,20-trihydroxyleukotriene B4
(CHEBI:134442)
has functional parent
leukotriene B4
(CHEBI:15647)
10,11-dihydro-20,20-dihydroxyleukotriene B4
(CHEBI:134437)
has functional parent
leukotriene B4
(CHEBI:15647)
12,20-dioxoleukotriene B4
(CHEBI:134520)
has functional parent
leukotriene B4
(CHEBI:15647)
12-dehydro-leukotriene B4
(CHEBI:27814)
has functional parent
leukotriene B4
(CHEBI:15647)
12-oxo-20-hydroxyleukotriene B4
(CHEBI:134456)
has functional parent
leukotriene B4
(CHEBI:15647)
18-hydroxy-18-oxo-dinorleukotriene B4
(CHEBI:63980)
has functional parent
leukotriene B4
(CHEBI:15647)
18-hydroxyleukotriene B4
(CHEBI:138201)
has functional parent
leukotriene B4
(CHEBI:15647)
19-hydroxyleukotriene B4
(CHEBI:138196)
has functional parent
leukotriene B4
(CHEBI:15647)
20,20,20-trihydroxyleukotriene B4
(CHEBI:134515)
has functional parent
leukotriene B4
(CHEBI:15647)
20,20-dihydroxyleukotriene B4
(CHEBI:134516)
has functional parent
leukotriene B4
(CHEBI:15647)
20-hydroxy-20-oxoleukotriene B4
(CHEBI:27562)
has functional parent
leukotriene B4
(CHEBI:15647)
20-hydroxy-leukotriene B4
(CHEBI:15646)
has functional parent
leukotriene B4
(CHEBI:15647)
leukotriene B4(1−)
(CHEBI:57461)
is conjugate base of
leukotriene B4
(CHEBI:15647)
|
|
(5S,6Z,8E,10E,12R,14Z)-5,12-dihydroxyicosa-6,8,10,14-tetraenoic acid
|
|
(5S,12R,6Z,8E,10E,14Z)-5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid
|
ChEBI
|
|
(5S,6Z,8E,10E,12R,14Z)-5,12-dihydroxyeicosa-6,8,10,14-tetraenoic acid
|
ChEBI
|
|
(S-(R*,S*-(E,Z,E,Z)))-5,12-Dihydroxy-6,8,10,14-eicosatetraenoic acid
|
ChemIDplus
|
|
5(S),12(R)-dihydroxy-6(Z),8(E),10(E),14(Z)-eicosatetraenoic acid
|
ChEBI
|
|
5(S),12(R)-dihydroxy-6(Z),8(E),10(E),14(Z)-icosatetraenoic acid
|
ChEBI
|
|
5,12-Dihete
|
ChEBI
|
|
5,12-Hete
|
ChemIDplus
|
|
5S,12R-diHETE
|
LIPID MAPS
|
|
5S,12R-dihydroxy-6Z,8E,10E,14Z-eicosatetraenoic acid
|
LIPID MAPS
|
|
Leukotriene B4
|
KEGG COMPOUND
|
|
LTB4
|
ChEBI
|
|
LTB4
|
ChemIDplus
|
|
LTB4
|
KEGG COMPOUND
|
|
4235309
|
Reaxys Registry Number
|
Reaxys
|
|
71160-24-2
|
CAS Registry Number
|
KEGG COMPOUND
|
|
71160-24-2
|
CAS Registry Number
|
ChemIDplus
|
Park D, Kwak DW, Kim JH (2021)
Leukotriene B4 receptors contribute to house dust mite-induced eosinophilic airway inflammation via TH2 cytokine production.
BMB reports 54, 182-187 [PubMed:33612149]
[show Abstract]
Leukotriene B4 (LTB4) is a lipid mediator of inflammation that is generated from arachidonic acid via the 5-lipoxygenase pathway. Previous studies have reported that the receptors of LTB4, BLT1, and BLT2 play mediatory roles in the allergic airway inflammation induced by ovalbumin (OVA). However, considering that house dust mites (HDMs) are the most prevalent allergen and well-known risk factor for asthmatic allergies, we are interested in elucidating the contributory roles of BLT1/2 in HDMinduced allergic airway inflammation. Our aim in this study was to investigate whether BLT1/2 play any roles in HDM-induced allergic airway inflammation. In this study, we observed that the levels of ligands for BLT1/2 [LTB4 and 12(S)-HETE (12(S)- hydroxyeicosatetraenoic acid)] were significantly increased in bronchoalveolar lavage fluid (BALF) after HDM challenge. Blockade of BLT1 or BLT2 as well as of 5-lipoxygenase (5-LO) or 12-lipoxygenase (12-LO) markedly suppressed the production of TH2 cytokines (IL-4, IL-5, and IL-13) and alleviated lung inflammation and mucus secretion in an HDM-induced eosinophilic airway-inflammation mouse model. Together, these results indicate that the 5-/12-LO-BLT1/2 cascade plays a role in HDMinduced airway inflammation by mediating the production of TH2 cytokines. Our findings suggest that BLT1/2 may be a potential therapeutic target for patients with HDM-induced allergic asthma. [BMB Reports 2021; 54(3): 182-187]. | Neves JAJ, De Matos MR, Ramalho T, Santos-Bezerra DP, Cavalcante CDGD, Alpino Peixoto R, Queiroz MS, Jancar S, Correa-Giannella ML (2020)
Increased leukotriene B4 plasma concentration in type 2 diabetes individuals with cardiovascular autonomic neuropathy.
Diabetology & metabolic syndrome 12, 99 [PubMed:33292560]
[show Abstract]
Background and aimA low-grade inflammation is associated with cardiac autonomic neuropathy (CAN) and increased concentration of leukotriene B4 (LTB4) was found in individuals with type 1 diabetes and definitive CAN. This cross-sectional study evaluated plasma concentration of LTB4 and of other inflammatory mediators, namely, tumor necrosis factor (TNF), interleukin (IL)1B, and IL10 in individuals with type 2 diabetes (T2D) and different degrees of CAN, and correlated these inflammatory mediators with the degree of glycemic control and with a surrogate marker of insulin resistance.MethodsTNF, IL1B, IL10 and LTB4 plasma concentrations were measured in 129 T2D subjects (62% women with [median] age of 63 years, disease duration of 8 years and HbA1c of 7.3%) with or without CAN. The Lipid accumulation product index was used as a surrogate marker of insulin resistance.ResultsLTB4 concentration was significantly higher in those presenting incipient CAN (69.7 ± 16.6 pg mL-1) and definitive CAN (71.5 ± 15.7 pg mL-1) versus those without CAN (57.0 ± 13.9 pg mL-1). The groups without CAN and with incipient CAN were pooled (group without definitive CAN) and compared to those with definitive CAN. LTB4 concentration was higher in the latter group, as well as TNF concentration, while IL10 concentration was lower in this group. After adjustment for confounding variables, only LTB4 concentration remained significantly different between the groups with and without definitive CAN. Plasma concentration of LTB4 did not correlate with the degree of glycemic control. After sorting the participants by sex, a borderline weak correlation was found between LTB4 and the Lipid accumulation product index in women.ConclusionIn the T2D setting, circulating LTB4 concentration seems to be associated with cardiovascular dysautonomia. | Lotfi R, Davoodi A, Mortazavi SH, Gorgin Karaji A, Tarokhian H, Rezaiemanesh A, Salari F (2020)
Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) in patients with allergic rhinitis.
Molecular biology reports 47, 7745-7754 [PubMed:32960415]
[show Abstract]
Timely and successful resolution of acute inflammation plays a crucial role in preventing the development of chronic airway inflammation in allergic rhinitis (AR). This study intends to assess the serum levels of pro-inflammatory leukotriene B4 (LTB4), anti-inflammatory mediators, including resolvin E1 (RvE1), RvD1, IL-10, and TGF-β, besides mRNA expression level of G-protein coupled receptor 120 (GPR120) and peroxisome proliferator-activated receptor-γ (PPAR-γ) receptors in peripheral blood leukocytes of AR patients. Thirty-seven AR patients and thirty age- and gender-matched healthy subjects were enrolled in this study. The serum levels of LTB4, RvE1, RvD1, IL-10, and TGF-β were measured using enzyme-linked immunosorbent assay (ELISA) technique, and the mRNA expression level of GPR120 and PPAR-γ was assessed by the real-time PCR method. The serum levels of RvE1 and LTB4 were significantly higher in patients with AR than in healthy subjects (P < 0.01 and P < 0.0001, respectively). However, a significantly lower ratio of RvE1 and RvD1 to LTB4 was found in patients with AR relative to healthy subjects (P < 0.05 and P < 0.0001, respectively). Likewise, the serum levels of both IL-10 and TGF-β cytokines were significantly reduced in patients with AR compared to healthy subjects (P < 0.01 and P < 0.0001, respectively). Furthermore, the mRNA expression of PPAR-γ was significantly lower in patients with AR than in healthy subjects (P < 0.05). Our findings indicate that imbalanced pro-resolving lipid mediator RvE1 and pro-inflammatory LTB4 might contribute to the defective airway inflammation-resolution and subsequent progression toward chronic inflammation in AR patients. | He R, Chen Y, Cai Q (2020)
The role of the LTB4-BLT1 axis in health and disease.
Pharmacological research 158, 104857 [PubMed:32439596]
[show Abstract]
Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflammatory diseases, such as infectious diseases, allergy, autoimmune diseases, and metabolic disease via mediating recruitment and/or activation of different types of inflammatory cells depending on different stages or the nature of inflammatory response. Recent studies also demonstrated that LTB4 acts on non-immune cells via BLT1 to initiate and/or amplify pathological inflammation in various tissues. In addition, emerging evidence reveals a complex role of the LTB4-BLT1 axis in cancer, either tumor-inhibitory or tumor-promoting, depending on the different target cells. In this review, we summarize both established understanding and the most recent progress in our knowledge about the LTB4-BLT1 axis in host defense, inflammatory diseases and cancer. | Roversi P, Ryffel B, Togbe D, Maillet I, Teixeira M, Ahmat N, Paesen GC, Lissina O, Boland W, Ploss K, Caesar JJ, Leonhartsberger S, Lea SM, Nunn MA (2013)
Bifunctional lipocalin ameliorates murine immune complex-induced acute lung injury.
The Journal of biological chemistry 288, 18789-18802 [PubMed:23625922]
[show Abstract]
Molecules that simultaneously inhibit independent or co-dependent proinflammatory pathways may have advantages over conventional monotherapeutics. OmCI is a bifunctional protein derived from blood-feeding ticks that specifically prevents complement (C)-mediated C5 activation and also sequesters leukotriene B4 (LTB4) within an internal binding pocket. Here, we examined the effect of LTB4 binding on OmCI structure and function and investigated the relative importance of C-mediated C5 activation and LTB4 in a mouse model of immune complex-induced acute lung injury (IC-ALI). We describe two crystal structures of bacterially expressed OmCI: one binding a C16 fatty acid and the other binding LTB4 (C20). We show that the C5 and LTB4 binding activities of the molecule are independent of each other and that OmCI is a potent inhibitor of experimental IC-ALI, equally dependent on both C5 inhibition and LTB4 binding for full activity. The data highlight the importance of LTB4 in IC-ALI and activation of C5 by the complement pathway C5 convertase rather than by non-C proteases. The findings suggest that dual inhibition of C5 and LTB4 may be useful for treatment of human immune complex-dependent diseases. | Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, Bandyopadhyay S, Jones KN, Kelly S, Shaner RL, Sullards CM, Wang E, Murphy RC, Barkley RM, Leiker TJ, Raetz CR, Guan Z, Laird GM, Six DA, Russell DW, McDonald JG, Subramaniam S, Fahy E, Dennis EA (2010)
Lipidomics reveals a remarkable diversity of lipids in human plasma.
Journal of lipid research 51, 3299-3305 [PubMed:20671299]
[show Abstract]
The focus of the present study was to define the human plasma lipidome and to establish novel analytical methodologies to quantify the large spectrum of plasma lipids. Partial lipid analysis is now a regular part of every patient's blood test and physicians readily and regularly prescribe drugs that alter the levels of major plasma lipids such as cholesterol and triglycerides. Plasma contains many thousands of distinct lipid molecular species that fall into six main categories including fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenols. The physiological contributions of these diverse lipids and how their levels change in response to therapy remain largely unknown. As a first step toward answering these questions, we provide herein an in-depth lipidomics analysis of a pooled human plasma obtained from healthy individuals after overnight fasting and with a gender balance and an ethnic distribution that is representative of the US population. In total, we quantitatively assessed the levels of over 500 distinct molecular species distributed among the main lipid categories. As more information is obtained regarding the roles of individual lipids in health and disease, it seems likely that future blood tests will include an ever increasing number of these lipid molecules. | Bhavsar PK, Levy BD, Hew MJ, Pfeffer MA, Kazani S, Israel E, Chung KF (2010)
Corticosteroid suppression of lipoxin A4 and leukotriene B4 from alveolar macrophages in severe asthma.
Respiratory research 11, 71 [PubMed:20529300]
[show Abstract]
BackgroundAn imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B4 (LTB4), and lipoxin A4 (LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids.MethodsAMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 microg/ml) with or without dexamethasone (10(-6)M). LTB4 and LXA4 were measured by enzyme immunoassay.ResultsLXA4 biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA4 induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB4 were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB4 was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB4 and LXA4, with lesser suppression of LTB4 in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA4 and FEV1 (% predicted) (r(s) = 0.60; p < 0.01).ConclusionsDecreased LXA4 and increased LTB4 generation plus impaired corticosteroid sensitivity of LPS-induced LTB4 but not of LXA4 support a role for AMs in establishing a pro-inflammatory balance in severe asthma. | Narala VR, Adapala RK, Suresh MV, Brock TG, Peters-Golden M, Reddy RC (2010)
Leukotriene B4 is a physiologically relevant endogenous peroxisome proliferator-activated receptor-alpha agonist.
The Journal of biological chemistry 285, 22067-22074 [PubMed:20400503]
[show Abstract]
Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play central roles in metabolism and inflammation. Although a variety of compounds have been shown to activate PPARs, identification of physiologically relevant ligands has proven difficult. In silico studies of lipid derivatives reported here identify specific 5-lipoxygenase products as candidate physiologically relevant PPAR-alpha activators. Subsequent studies show both in vitro and in a murine model of inflammation that 5-lipoxygenase stimulation induces PPAR-alpha signaling and that this results specifically from production of the inflammatory mediator and chemoattractant leukotriene B(4) (LTB(4)). Activation of PPAR-alpha is a direct effect of intracellularly generated LTB(4) binding to the nuclear receptor and not of secreted LTB(4) acting via its cell-surface receptors. Activation of PPAR-alpha reduces secretion of LTB(4) by stimulating degradation of this fatty acid derivative. We also show that the LTB(4) precursors leukotriene A(4) (LTA(4)) and 5-hydroperoxyeicosatetrenoic acid (5-HPETE) activate PPAR-alpha but have no significant endogenous effect independent of conversion to LTB(4). We conclude that LTB(4) is a physiologically relevant PPAR-alpha activator in cells of the immune system. This, together with previous findings, demonstrates that different types of lipids serve as endogenous PPAR-alpha ligands, with the relevant ligand varying between functionally different cell types. Our results also support the suggestion that regulation of inflammation may involve balancing proinflammatory effects of LTB(4), exerted through cell-surface receptors, and anti-inflammatory effects exerted through PPAR-alpha activation. | Flamand L, Tremblay MJ, Borgeat P (2007)
Leukotriene B4 triggers the in vitro and in vivo release of potent antimicrobial agents.
Journal of immunology (Baltimore, Md. : 1950) 178, 8036-8045 [PubMed:17548641]
[show Abstract]
Leukotriene B(4) (LTB(4)) is a bioactive lipid derived from the metabolism of arachidonic acid. Mainly produced by polymorphonuclear leukocytes (PMN) and macrophages, LTB(4) triggers several functional responses important in host defense, including the secretion of lysosomal enzymes, the activation of NADPH oxidase activity, NO formation, and phagocytosis. We report that LTB(4), but not structural analogs thereof, stimulates primed human PMN to release molecules having potent antimicrobial activities. Exposure of bacteria (Escherichia coli and Staphylococcus aureus) or viruses (herpes simplex virus type 1 and HIV type 1) to supernatants of LTB(4)-activated PMN led to > or =90% reduction in infectivity. ELISA and mass spectroscopy analysis of proteins released from LTB(4)-activated PMN have identified several antimicrobial proteins, including alpha-defensins, cathepsin G, elastase, lysozyme C, and LL-37, that are likely to participate in the killing of microorganisms. In addition to these in vitro observations, i.v. injections of LTB(4) (50 microg/kg) to monkeys led to an increase in alpha-defensin plasmatic levels and enhanced ex vivo antimicrobial activities of plasma. These results demonstrate the ability of LTB(4) to cause the release of potent antimicrobial agents from PMN in vitro as well as in vivo and add further support to the important role of LTB(4) in host defense. | Bäck M, Sakata K, Qiu H, Haeggström JZ, Dahlén SE (2007)
Endothelium-dependent vascular responses induced by leukotriene B4.
Prostaglandins & other lipid mediators 83, 209-212 [PubMed:17481557]
[show Abstract]
Leukotriene B(4) (LTB(4)) is an inflammatory mediator derived from the 5-lipoxygenase pathway of arachidonic acid metabolism and has recently implicated in the pathogenesis of atherosclerosis. There are two membrane bound receptors for LTB(4): BLT(1) and BLT(2), which represent the high and low affinity receptors, respectively. BLT receptors are expressed on leukocytes, and LTB(4) is a potent chemoattractant for neutrophils, eosinophils, and T lymphocytes. Recent studies have in addition shown that LTB(4) is an indirectly acting vasoconstrictor of isolated vascular preparations. In the guinea pig aorta, the LTB(4)-induced contractions were inhibited by endothelium-denudation. In addition, pre-treatment with the NO synthase inhibitor, L-NOARG, significantly enhanced the contractions induced by LTB(4). The contractile response induced by LTB(4) in the guinea pig aorta was abolished by the selective BLT(1) receptor antagonist U75302 and the expression of BLT(1) receptor mRNA in the guinea pig aorta was established by RT-PCR. Taken together, these results suggest that LTB(4) activates BLT(1) receptors on the endothelium of the guinea pig aorta, associated with the release of both contractile factors and NO. | Murphy RC, Gijón MA (2007)
Biosynthesis and metabolism of leukotrienes.
The Biochemical journal 405, 379-395 [PubMed:17623009]
[show Abstract]
Leukotrienes are metabolites of arachidonic acid derived from the action of 5-LO (5-lipoxygenase). The immediate product of 5-LO is LTA4 (leukotriene A4), which is enzymatically converted into either LTB4 (leukotriene B4) by LTA4 hydrolase or LTC4 (leukotriene C4) by LTC4 synthase. The regulation of leukotriene production occurs at various levels, including expression of 5-LO, translocation of 5-LO to the perinuclear region and phosphorylation to either enhance or inhibit the activity of 5-LO. Several other proteins, including cPLA2a (cytosolic phospholipase A2a) and FLAP (5-LO-activating protein) also assemble at the perinuclear region before production of LTA4. LTC4 synthase is an integral membrane protein that is present at the nuclear envelope; however, LTA4 hydrolase remains cytosolic. Biologically active LTB4 is metabolized by w-oxidation carried out by specific cytochrome P450s (CYP4F) followed by b-oxidation from the w-carboxy position and after CoA ester formation. Other specific pathways of leukotriene metabolism include the 12-hydroxydehydrogenase/15-oxo-prostaglandin-13-reductase that forms a series of conjugated diene metabolites that have been observed to be excreted into human urine. Metabolism of LTC4 occurs by sequential peptide cleavage reactions involving a g-glutamyl transpeptidase that forms LTD4 (leukotriene D4) and a membrane-bound dipeptidase that converts LTD4 into LTE4 (leukotriene E4) before w-oxidation. These metabolic transformations of the primary leukotrienes are critical for termination of their biological activity, and defects in expression of participating enzymes may be involved in specific genetic disease. | Chen M, Lam BK, Kanaoka Y, Nigrovic PA, Audoly LP, Austen KF, Lee DM (2006)
Neutrophil-derived leukotriene B4 is required for inflammatory arthritis.
The Journal of experimental medicine 203, 837-842 [PubMed:16567388]
[show Abstract]
Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption. | Bäck M, Qiu H, Haeggström JZ, Sakata K (2004)
Leukotriene B4 is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor.
American journal of physiology. Heart and circulatory physiology 287, H419-24 [PubMed:15016629]
[show Abstract]
Leukotriene B(4) (LTB(4)) is a potent leukocyte chemoattractant recently implicated in the pathogenesis of atherosclerosis. The aim of this study was to assess the effects of LTB(4) on isolated aortic preparations. Rings of guinea pig aorta were challenged with LTB(4) for recording mechanical responses and measurements of mediator release, and LTB(4) receptor (BLT(1)) expression was assessed by RT-PCR. Single concentrations of LTB(4) induced concentration-dependent contractions that were inhibited by treatment with antihistamines, indomethacin, or the thromboxane receptor antagonist BAYu3405 as well as by denudation of endothelium. In addition, LTB(4) increased the release of histamine and thromboxane in the bath. The contractions induced by LTB(4) were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BLT(1) receptor antagonist U-75302. Pretreatment with all-trans-retinoic acid enhanced the contractions and the release of histamine induced by LTB(4), without affecting either the contractions induced by histamine or the histamine release evoked by calcium ionophore A23187. Analysis by RT-PCR indicated the expression of a BLT(1) receptor in the guinea pig aorta and that BLT(1) receptor mRNA was upregulated after treatment with retinoic acid. These results suggest that LTB(4) contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BLT(1) receptor-mediated response can be upregulated by all-trans-retinoic acid. | Bentancur AG, Naveh N, Lancri J, Selah BA, Livneh A (2004)
Urine leukotriene B4 in familial Mediterranean fever.
Clinical and experimental rheumatology 22, S56-8 [PubMed:15515787]
[show Abstract]
ObjectiveTo determine urinary leukotriene B4 (LTB4) levels and their role in FMF:MethodsUrinary LTB4 levels were studied using a commercial ELISA kit in 12 FMF patients during abdominal attacks, and 20 FMF patients during remission.ResultsUrinary LTB4 levels in FMF patients during attacks were comparable to those during remission, but higher than normal levels (p = 0.03).ConclusionsThese findings suggest a persistent activation of the leukotriene pathway in FMF. Whether elevated LTB4 levels are the cause or the effect of inflammation is yet to be determined. | Lambiase A, Bonini S, Rasi G, Coassin M, Bruscolini A, Bonini S (2003)
Montelukast, a leukotriene receptor antagonist, in vernal keratoconjunctivitis associated with asthma.
Archives of ophthalmology (Chicago, Ill. : 1960) 121, 615-620 [PubMed:12742837]
[show Abstract]
ObjectiveTo evaluate the effects on signs and symptoms of a coexisting vernal keratoconjunctivitis in patients treated with oral montelukast sodium for asthma.MethodsTwelve patients with vernal keratoconjunctivitis and asthma were enrolled in this pilot study. Topical eyedrops or any systemic treatment was discontinued for at least 7 days before montelukast treatment. Patients were asked to grade their ocular discomfort daily. The following signs and symptoms were also recorded and graded through medical examination at baseline,after 15 days of treatment, and 15 days after treatment discontinuation: physician-evaluated tarsal and bulbar papillae, hyperemia, secretion, and chemosis; and patient-evaluated itching, burning, tearing, photophobia, foreign body sensation, secretion, and redness. Peak expiratory flow rate at 8 AM was also recorded. Samples were collected at the same time points for enzyme-linked immunosorbent assay measurement of leukotriene B4 in tears and leukotriene E4 in urine.ResultsEight of the 10 patients evaluated reported a reduction in symptoms at the end of treatment. Montelukast treatment significantly decreased physician-rated hyperemia, secretion, and chemosis as well as patient-rated burning, tearing, photophobia, secretion, and redness. Effects persisted 15 days after discontinuation of treatment. Clinical changes were associated with a significant increase in leukotriene B4 in tears and a significant decrease in leukotriene E4 in urine after 15 days of treatment.ConclusionThe significant and persistent reduction of ocular signs and symptoms in asthmatic patients with vernal keratoconjunctivitis treated for 15 days with montelukast strongly suggests the need for double-masked placebo-controlled trials to confirm the potential of this new treatment in vernal keratoconjunctivitis. | Friedrich EB, Tager AM, Liu E, Pettersson A, Owman C, Munn L, Luster AD, Gerszten RE (2003)
Mechanisms of leukotriene B4--triggered monocyte adhesion.
Arteriosclerosis, thrombosis, and vascular biology 23, 1761-1767 [PubMed:12947016]
[show Abstract]
ObjectiveLeukotriene B4 (LTB4) has been implicated in the trafficking of monocytes to inflammatory pathologic conditions, such as transplant rejection and atherosclerosis. The aim of this study was to determine the mechanisms by which LTB4 contributes to monocyte capture from the circulation.Methods and resultsIn in vitro and in vivo vascular models, the lipid chemoattractant LTB4 was an equipotent agonist of monocyte adhesion compared with the chemokine monocyte chemoattractant protein-1 (MCP-1). Adenoviral gene transfer of specific endothelial adhesion molecules and blocking monoclonal antibody studies demonstrated that LTB4 triggers both beta1- and beta2-integrin-dependent adhesion. Flow cytometry studies suggested that changes in integrin avidity or affinity, rather than alterations of integrin surface expression, were responsible for the chemoattractant-triggered arrest. Surprisingly, in contrast to the peptide chemokine MCP-1, LTB4 did not activate the phosphoinositide 3-kinase pathway, which is a functionally critical step in chemokine-triggered effector functions.ConclusionsLTB4 is a potent trigger of monocyte adhesion under flow yet mediates its effects via pathways that appear to differ from peptide chemoattractants. A better understanding of the mechanisms of LTB4-induced monocyte trafficking might shed insight into disease pathogenesis and pinpoint critical steps for therapeutic intervention for multiple human inflammatory pathologic conditions. | Berry KA, Borgeat P, Gosselin J, Flamand L, Murphy RC (2003)
Urinary metabolites of leukotriene B4 in the human subject.
The Journal of biological chemistry 278, 24449-24460 [PubMed:12709426]
[show Abstract]
Leukotriene B4 (LTB4) is a potent chemoattractant for neutrophils and is thought to play a role in a variety of inflammatory responses in humans. The metabolism of LTB4 in vitro is complex with several competing pathways of biotransformation, but metabolism in vivo, especially for normal human subjects, is poorly understood. As part of a Phase I Clinical Trial of human tolerance to LTB4, four human subjects were injected with 150 nmol/kg LTB4 with one additional subject as placebo control. The urine of the subjects was collected in two separate pools (0-6 and 7-24 h), and aliquots from these urine collections were analyzed using high performance liquid chromatography, UV spectroscopy, and negative ion electrospray ionization tandem mass spectrometry for metabolites of LTB4. In the current investigation, 11 different metabolites of LTB4 were identified in the urine from those subjects injected with LTB4, and none were present in the urine from the placebo-injected subject. The unconjugated LTB4 metabolites found in urine were structurally characterized as 18-carboxy-LTB4, 10,11-dihydro-18-carboxy-LTB4, 20-carboxy-LTB4, and 10,11-dihydro-20-carboxy-LTB4. Several glucuronide-conjugated metabolites of LTB4 were characterized including 17-, 18-, 19-, and 20-hydroxy-LTB4, 10-hydroxy-4,6,12-octadecatrienoic acid, LTB4, and 10,11-dihydro-LTB4. The amount of LTB4 glucuronide (16.7-29.4 pmol/ml) and 20-carboxy-LTB4 (18.9-30.6 pmol/ml) present in the urine of subjects injected with LTB4 was determined using an isotope dilution mass spectrometric assay before and after treatment of the urine samples with beta-glucuronidase. The urinary metabolites of LTB4 identified in this investigation were excreted in low amounts, yet it is possible that one or more of these metabolites could be used to assess LTB4 biosynthesis following activation of the 5-lipoxygenase pathway in vivo. | Mancuso P, Nana-Sinkam P, Peters-Golden M (2001)
Leukotriene B4 augments neutrophil phagocytosis of Klebsiella pneumoniae.
Infection and immunity 69, 2011-2016 [PubMed:11254552]
[show Abstract]
Neutrophils play a critical role in the clearance of bacteria from the lung and other organs by their capacity for phagocytosis and killing. Previously, we identified an important role for the leukotrienes in rat alveolar macrophage phagocytosis of Klebsiella pneumoniae. In this report, we explored the possibility that the leukotrienes play an important role in phagocytosis by neutrophils as well. Inhibition of endogenous leukotriene synthesis by 5-lipoxygenase knockout in mice or by pharmacologic means in human peripheral blood neutrophils attenuated phagocytosis of opsonized K. pneumoniae. Reduced phagocytosis was also observed in human neutrophils pretreated with a leukotriene B4 receptor but not a cysteinyl-leukotriene receptor antagonist. While leukotriene B4 reconstituted defective phagocytosis in leukotriene-deficient neutrophils and enhanced phagocytosis in neutrophils capable of leukotriene synthesis, leukotriene C4, leukotriene D4, 5-hydroperoxyeicosatetraenoic acid, and 5-oxo-eicosatetraenoic acid were ineffective. To determine the opsonin dependence of the leukotriene B4 augmentation of phagocytosis, we assessed the ability of leukotriene B4 to modulate neutrophil phagocytosis and the adherence of sheep erythrocytes opsonized with immunoglobulin G or the complement fragment C3bi. While leukotriene B4 augmented both Fc receptor- and complement receptor-mediated phagocytosis, increased adherence to leukotriene B4-treated neutrophils was limited to complement opsonized targets. In conclusion, we have identified a novel role for leukotriene B4 in the augmentation of neutrophil phagocytosis mediated by either the Fc or complement receptor. | Willemsen MA, Rotteveel JJ, de Jong JG, Wanders RJ, IJlst L, Hoffmann GF, Mayatepek E (2001)
Defective metabolism of leukotriene B4 in the Sjögren-Larsson syndrome.
Journal of the neurological sciences 183, 61-67 [PubMed:11166796]
[show Abstract]
The Sjögren-Larsson Syndrome (SLS) is a neurocutaneous disorder, caused by deficient activity of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH). FALDH catalyzes the oxidation of medium- and long-chain fatty aldehydes to their corresponding carboxylic acids. SLS is diagnosed by demonstrating the enzyme deficiency or by mutation analysis of the FALDH gene, while laboratory investigations of plasma, urine, and cerebrospinal fluid do not reveal any diagnostic abnormality. Leukotriene (LT) B4 is a pro-inflammatory mediator synthesized from arachidonic acid. LTB4 is inactivated by microsomal omega-oxidation, successively yielding 20-OH-LTB4, 20-CHO-LTB4 and 20-COOH-LTB4. Since FALDH is involved in LTB4 degradation, we have analyzed LTB4 and its metabolites in urine and cerebrospinal fluid as well as the degradation capacity for LTB4 in fresh polymorphonuclear leukocytes (PMN) of SLS patients. The urinary concentrations of LTB4, 20-OH-LTB4 and 20-COOH-LTB4 are below the detection limit in healthy controls. The urine of all SLS patients (n=13) exhibited highly elevated concentrations of LTB4 and 20-OH-LTB4, while 20-COOH-LTB4 was absent. Cerebrospinal fluid levels of LTB4, 20-OH-LTB4 and 20-COOH-LTB4 were found to be normal (n=7). PMN isolated from four patients were shown to be unable to convert 20-OH-LTB4 to 20-COOH-LTB4. Our findings provide unambiguous evidence for defective LTB4 degradation in SLS patients, and offer new and non-invasive diagnostic tools. Moreover, they open new pathophysiological considerations, with the prospect of rational treatment strategies. | Emingil G, Coker I, Atilla G, Hüseyinov A (2000)
Levels of leukotriene B4 and platelet activating factor in gingival crevicular fluid in renal transplant patients receiving cyclosporine A.
Journal of periodontology 71, 50-57 [PubMed:10695938]
[show Abstract]
BackgroundCyclosporine A (CsA) is a potent immunosuppressant effectively used to prevent organ transplant rejection and also to treat several systemic diseases. CsA-induced gingival overgrowth (CsA GO) is the most widely seen side effect of this drug; its pathogenesis is not completely understood. The aim of the present study was to identify the role of leukotriene B4 (LTB4) and platelet activating factor (PAF) in the pathogenesis of CsA GO.MethodsLTB4 and PAF levels were detected in gingival crevicular fluid (GCF) samples from renal transplant patients receiving CsA therapy and exhibiting CsA GO, from patients with gingivitis and from periodontally healthy subjects. Plaque index, papilla bleeding index, and hyperplastic index were recorded at each study site. GCF samples and clinical data were obtained from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. LTB4 was extracted from the samples by solid-phase method using C18 cartridge and purified by high-performance liquid chromatographic (HPLC) method and analyzed by radioimmunoassay (RIA). PAF was extracted from GCF samples passing through amberlit resin columns, purified by HPLC, and analyzed by RIA.ResultsTotal amounts of LTB4 and PAF in GCF were higher in CsA GO+ sites compared to the healthy sites from healthy controls. However, the amount of LTB4 and PAF elevation in CsA GO+ sites was not significantly higher than those in diseased sites. Clinical degrees of gingival inflammation were also similar between CsA GO+ and diseased sites. LTB4 and PAF total amounts in GCF were higher in CsA GO+ sites compared to CsA GO- sites in the same subjects, but this difference just failed to reach significance. Similar findings were obtained with concentration data.ConclusionsThe results of this study indicate that CsA therapy does not have a significant effect on GCF LTB4 and PAF levels and that gingival inflammation seems to be the main reason for their elevation. In CsA-treated patients, alterations in LTB4 and PAF levels might play a role in CsA GO through some asyet unknown mechanism. To our knowledge, this is the first report describing the levels of lipid mediators in GCF of CsA-treated patients. We assume that further studies will contribute to the understanding of the pathogenesis of CsA-induced gingival overgrowth. | Crocker I, Lawson N, Daniels I, Baker P, Fletcher J (1999)
Significance of fatty acids in pregnancy-induced immunosuppression.
Clinical and diagnostic laboratory immunology 6, 587-593 [PubMed:10391868]
[show Abstract]
Pregnancy can exert suppressive effects on chronic inflammatory conditions. We have previously demonstrated a depression in polymorphonuclear leukocyte (PMN) respiratory burst during pregnancy which could explain this amelioration. To elucidate the biochemical mechanism, we have examined PMN phospholipase A2 (PLA2) activity and its relationship to cellular and circulating fatty acids in pregnant women (30 to 34 weeks) and nonpregnant controls. PMN PLA2 activity was determined by arachidonic acid (AA) and leukotriene B4 (LTB4) release, respiratory burst activity was determined by lucigenin-enhanced chemiluminescence, and total serum and PMN fatty acid levels were determined by gas-liquid chromatography. AA release was significantly reduced for pregnancy PMNs in response to N-formyl-met-leu-phe (fMLP) under unprimed and tumor necrosis factor alpha (TNF-alpha)- or interleukin 8-primed conditions. Similarly, LTB4 liberation was significantly reduced in response to fMLP and phorbol myristate acetate in unprimed and TNF-alpha-primed pregnancy PMNs. All major fatty acid classes were altered in the pregnant state. Of these differences in PMNs, oleic acid and alpha-linolenic acid showed a significant increase (13 and 26%, respectively) and stearic acid and AA showed a significant decrease (8 and 30%, respectively). The stearic acid, oleic acid, and AA compositions of all cells analyzed correlated with their corresponding changes in serum fatty acid levels. Crossover serum incubations modified both fatty acid profiles and the PMN respiratory burst accordingly, while individual fatty acid incorporation studies highlighted the importance of polyunsaturated fatty acids for NADPH oxidase efficiency. These findings indicate that the attenuation of PMN function in pregnancy may originate from a reduction in the available pool of cellular fatty acids. Furthermore, this reduction arises as a direct result of a pregnancy-induced shift in circulating fatty acids from polyunsaturated to monounsaturated forms. | Garcia-Pastor P, Randazzo A, Gomez-Paloma L, Alcaraz MJ, Paya M (1999)
Effects of petrosaspongiolide M, a novel phospholipase A2 inhibitor, on acute and chronic inflammation.
The Journal of pharmacology and experimental therapeutics 289, 166-172 [PubMed:10087000]
[show Abstract]
The marine product petrosaspongiolide M is a novel inhibitor of phospholipase A2 (PLA2), showing selectivity for secretory PLA2 versus cytosolic PLA2, with a potency on the human synovial enzyme (group II) similar to that of manoalide. This compound was more potent than manoalide on bee venom PLA2 (group III) and had no effect on group I enzymes (Naja naja and porcine pancreatic PLA2). Inhibition of PLA2 was also observed in vivo in the zymosan-injected rat air pouch, on the secretory enzyme accumulated in the pouch exudate. Petrosaspongiolide M decreased carrageenan paw edema in mice after the oral administration of 5, 10, or 20 mg/kg. This marine metabolite (0.01-1.0 micromol/pouch) induced a dose-dependent reduction in the levels of prostaglandin (PG)E2, leukotriene B4, and tumor necrosis factor-alpha in the mouse air pouch injected with zymosan 4 h after the stimulus. It also had a weaker effect on cell migration. The inflammatory response of adjuvant arthritis was reduced by petrosaspongiolide M, which also inhibited leukotriene B4 levels in serum and PGE2 levels in paw homogenates. In contrast with indomethacin, this marine compound did not reduce PGE2 levels in stomach homogenates. Petrosaspongiolide M is a new inhibitor of secretory PLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic inflammation. | Seyger MM, van Pelt JP, van den Born J, Latijnhouwers MA, de Jong EM (1997)
Epicutaneous application of leukotriene B4 induces patterns of tenascin and a heparan sulfate proteoglycan epitope that are typical for psoriatic lesions.
Archives of dermatological research 289, 331-336 [PubMed:9209678]
[show Abstract]
Application of leukotriene B4 (LTB4) to normal human skin induces changes similar to those found in psoriatic skin, and it has proved to be a useful model for studying the pathogenesis and treatment of psoriasis. We studied the expression patterns of molecules that have recently been shown to be altered in lesional psoriatic skin, including the extracellular matrix protein tenascin (TN) and the basement membrane and cell surface-associated heparan sulfate proteoglycans (HSPGs). During 72-h the expression of these markers was studied immunohistochemically and the expression of TN was correlated with epidermal proliferation and influx of inflammatory cells. Following the peak influx of polymorphonuclear leukocytes, a marked increase in TN expression was noted in the papillary dermis 72 h after LTB4 application. The expression patterns of basal membrane-associated epitopes of HSPG remained unaltered, whereas the expression of cell surface-associated HSPG disappeared 72 h after LTB4 application. A significant correlation was found between dermal TN expression and epidermal hyperproliferation, and between TN expression and the presence of dermal T cells. These findings indicate that the model of LTB4-induced acute cutaneous inflammation displays many characteristics of early psoriatic lesions and could serve as a model to study some of the cell biological changes in this disease. | Shindo K, Koide K, Fukumura M (1997)
Enhancement of leukotriene B4 release in stimulated asthmatic neutrophils by platelet activating factor.
Thorax 52, 1024-1029 [PubMed:9516893]
[show Abstract]
BackgroundThe role of platelet activating factor (PAF) in asthma remains controversial. The priming effect of PAF on leukotriene B4 (LTB4) release, 5-lipoxygenase activity, and intracellular calcium levels in asthmatic neutrophils was examined.MethodsLTB4 and other lipoxygenase metabolites in neutrophils obtained from 17 asthmatic patients and 15 control subjects were measured by reverse phase-high performance liquid chromatography (RP-HPLC). Intracellular calcium levels were monitored using the fluorescent probe fura-2.ResultsThe mean (SD) basal LTB4, release from neutrophils was not significantly different between the two groups (0.05 (0.01) vs 0.03 (0.02) ng/10(6) cells); however, when stimulated with calcium ionophore A23187 (2.5 microM), neutrophils from asthma patients released more LTB4 than cells from control subjects (15.7 (1.2) vs 9.9 (1.6) ng/10(6) cells). Although PAF alone did not alter LTB4 release, it enhanced the response to subsequent A23187 stimulation. This effect was observed following treatment for five minutes with PAF at concentrations > 1.0 microM. The maximal effect was seen with 5.0 microM PAF + 2.5 microM A23187 (62.7 (2.2) vs 18.6 (2.3) ng/10(6) cells). Pretreatment with PAF also increased 5-lipoxygenase activity and intracellular calcium levels in neutrophils from asthmatic patients to a greater extent than in those from non-asthmatic patients.ConclusionsThese findings indicate that, in neutrophils from asthmatic patients, PAF enhances LTB4 release and increases 5-lipoxygenase activity and intracellular calcium to a greater extent than in neutrophils from non-asthmatic patients. | Mozalevskiĭ AF, Travianko TD, Iakovlev AA, Smirnova EA, Novikova NP, Sapa IIu (1997)
[Content of arachidonic acid metabolites in blood and saliva of children with bronchial asthma].
Ukrainskii biokhimicheskii zhurnal (1978) 69, 162-168 [PubMed:9606840]
[show Abstract]
The rise of the thromboxane B2, leukotriene B4 and prostaglandin F2a concentration in the blood and saliva of children was revealed during the attack of the bronchial asthma. At the same time the content of the prostaglandin E2 and prostacyclin in these biological fluids was reduced. The level of the eicosanoids in the examined liquids was correlated with the severity of bronchial asthma proceeding and with the adrenal glands function, which activity was also reduced. | Nathan H, Naveh N, Meyer E (1994)
Levels of prostaglandin E2 and leukotriene B4 in tears of vernal conjunctivitis patients during a therapeutic trial with indomethacin.
Documenta ophthalmologica. Advances in ophthalmology 85, 247-257 [PubMed:7924852]
[show Abstract]
A therapeutic trial of 1% indomethacin (Indoptic) eye drops was carried out in 21 children. Looking for possible mediators of inflammation in vernal conjunctivitis, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4 levels in the tears of 9 patients were measured and the effect of the treatment on them examined. A control group of 10 unaffected children was added. Out of 42 eyes in which indomethacin treatment was instilled, only 17 remained in treatment through a 6-week follow-up period. In a few of them a moderate improvement was obtained. The mean level of PGE2 in the patients before treatment was found to be slightly lower than that in the control group, and it dropped even lower during treatment. The average LTB4 level found in patients before treatment was significantly higher than the control group; it decreased somewhat following treatment, but not significantly. This is the first report of elevated LTB4 levels in vernal conjunctivitis, previously not recorded in the literature, it points to the possible role of LTB4 in the pathogenesis of the disease. A constant relationship was observed between low PGE2 levels and high LTB4 content in the patients' tears during highly inflamed states of the eye. We conclude that: (a) indomethacin did not prove to be a highly effective topical treatment for vernal conjunctivitis; (b) PGE2 does not seem to be a dominant mediator of inflammation in this disease; and (c) LTB4, on the other hand, apparently has a role in the mechanism of inflammation of the disease, thus raising hopes for future addition to therapy. | Soyombo O, Spur BW, Soh C, Lee TH (1993)
Structure/activity relationship of leukotriene B4 and its structural analogues in chemotactic, lysosomal-enzyme release and receptor-binding assays.
European journal of biochemistry 218, 59-66 [PubMed:8243477]
[show Abstract]
The biological activities of chemically synthesized leukotriene B4 and eight structural analogues have been studied using chemotaxis, lysosomal-enzyme release and receptor-binding assays on human neutrophils. The results show that increasing the number of double bonds between C14 and C20, having triple bonds at C6 or C14, substitution of the primary carboxyl group at C1, changing the geometry of the double bond at C6 from the cis to trans configuration and changing the chirality of the hydroxyl group at C12 from the R to the S configuration result in substantial loss of both biological activity and the capacity to bind to the LTB4 recognition site in parallel. We suggest that the functional epitopes of 5S,12R-dihydroxy-6,14-cis-8,10-trans-icosatetraenoic acid (LTB4) are either the same, or reside in the same domain as the binding site for the LTB4 receptor. Development of LTB4 antagonists to the high-affinity LTB4 receptor, based on the structure of LTB4, is unlikely to be successful. | Yanagisawa Y, Nagai T (1993)
[The relationship between serum leukotriene B4 and smoking].
Nihon eiseigaku zasshi. Japanese journal of hygiene 48, 698-706 [PubMed:8397308]
[show Abstract]
Leukotriene B4 (LTB4), an arachidonic acid metabolite released by neutrophils, is involved in the regulation of the host immune response to antigenic stimulation. Furthermore, LTB4 affects the chemokinesis, aggregation, and enzyme release of neutrophils and stimulates activity of cytotoxic T cells, natural killer cells and suppressor T cells. On the other hand, smoking typically results in inflammatory stimulation of the lung, and long-term smoking can cause chronic stimulation. In this paper, we report the measurement of LTB4, IgG, IgA, IgM, IgD and IgE in sera of cigarette smokers who did not have an allergic reaction (group 1), non-smokers who also had no history of allergy (group 2) and non-smokers who had delicate allergic conditions (group 3). The mean LTB4 concentration in serum of group 1 was nearly 3.3-fold greater than in group 2 and 2-fold greater than in group 3, being 430 +/- 55 (Mean +/- S.D.), 130 +/- 22 and 220 +/- 14 pg/ml, respectively. Concentrations of IgG, IgA, IgM, IgD and IgE of all volunteers were in the normal healthy range. The mean concentration of IgE in the serum of group 1 did not change significantly within one day. It was 35 +/- 4 IU/ml in the morning, 34 +/- 4 IU/ml in the afternoon, 31 +/- 2 IU/ml in the evening and 32 +/- 4 IU/ml the next morning. But in group 3 the IgE concentration changed significantly within one day, being < 25 IU/ml in the morning, 97 +/- 7 IU/ml in the afternoon, 97 +/- 7 IU/ml in the evening and 25 +/- 14 IU/ml the next morning.(ABSTRACT TRUNCATED AT 250 WORDS) | Iversen L, Fogh K, Ziboh VA, Kristensen P, Schmedes A, Kragballe K (1993)
Leukotriene B4 formation during human neutrophil keratinocyte interactions: evidence for transformation of leukotriene A4 by putative keratinocyte leukotriene A4 hydrolase.
The Journal of investigative dermatology 100, 293-298 [PubMed:8382716]
[show Abstract]
In the present study, keratinocytes were coincubated with human neutrophils to determine whether or not an increase in leukotriene B4 formation can occur. Human keratinocytes used were cultured in serum-free, low-calcium medium, whereas neutrophils were purified from heparinized venous blood. After coincubations, formation of leukotriene B4 was determined by reversed-phase high-performance liquid chromatography, coupled with its characteristic UV scan. Confirmation and quantification was by radioimmunoassay. Our data revealed that incubations of keratinocytes (1.5 x 10(6)) alone stimulated with calcium ionophore resulted in no detectable amounts of leukotriene B4. In contrast, incubations of neutrophils (5 x 10(6)) alone resulted in the generation of 62.2 +/- 8.5 ng of LTB4. Coincubations of the neutrophils with keratinocytes (ratio 3:1) resulted in a 56-163% increase in leukotriene B4 formation. To delineate the source of the newly formed leukotriene B4, incubations of keratinocytes with leukotriene A4 revealed that keratinocytes can transform leukotriene A4 into leukotriene B4. These latter findings indicate that although keratinocytes cannot directly metabolize arachidonic acid into leukotriene B4 via the 5-lipoxygenase enzyme, they can transform neutrophil-derived leukotriene A4 into leukotriene B4, thus indicating the possible existence of a putative keratinocyte-leukotriene A4 hydrolase. It is therefore reasonable to speculate that the keratinocytes possess the capacity to generate leukotriene B4 in the epidermis when provided leukotriene A4 and thereby can amplify the inflammatory processes occurring during neutrophil exocytosis. These findings indicate that transcellular metabolism of arachidonic acid metabolites in the epidermis by keratinocytes and neutrophils may contribute to the high levels of leukotriene B4 in lesional skin of inflammatory skin diseases. | Nieminen MM, Moilanen EK, Koskinen MO, Karvonen JI, Tuomisto L, Metsä-Ketelä TJ, Vapaatalo H (1992)
Inhaled budesonide fails to inhibit the PAF-induced increase in plasma leukotriene B4 in man.
British journal of clinical pharmacology 33, 645-652 [PubMed:1327049]
[show Abstract]
1. We studied the ability of inhaled budesonide to modulate PAF-induced acute effects in nine healthy nonsmoking volunteers. Responses in inflammatory cells and mediators in peripheral blood as well as in pulmonary function and circulation were monitored. 2. Inhalation of increasing doses of PAF (total cumulative dose of 500 micrograms) caused a rapid and profound decrease in circulating white blood cells, especially in granulocytes (P less than 0.01), which was turned to an increased number of these cells (P less than 0.05, P less than 0.025, respectively) in the blood samples taken 8 min after completion of the PAF challenge. No changes in the circulating platelets or their thromboxane production were found. Plasma concentrations of histamine or methylhistamine remained unchanged during PAF-inhalation, while plasma LTB4 tripled from the baseline level at 10 min (P less than 0.0005) and was returned to the pre-PAF value at 60 min. 3. PAF inhalation induced a bronchial obstruction (P less than 0.025), but no bronchial hyperresponsiveness to methacholine was found in any of our subjects when measured 24 h after the PAF challenge. Furthermore, PAF caused a decrease in systolic blood pressure (P less than 0.05). 4. Budesonide pretreatment of 400 micrograms twice daily during the preceding 5 days had no effect on any PAF-induced events measured in our study. That fact may also contradict the role of bronchial resident or alveolar cells as a source of the PAF-induced LTB4 burst in plasma. 5. We conclude that in healthy volunteers inhaled PAF induces a marked increase in plasma LTB4, which is not inhibited by inhaled budesonide.(ABSTRACT TRUNCATED AT 250 WORDS) | Pacheco Y, Hosni R, Chabannes B, Gormand F, Moliere P, Grosclaude M, Piperno D, Lagarde M, Perrin-Fayolle M (1992)
Leukotriene B4 level in stimulated blood neutrophils and alveolar macrophages from healthy and asthmatic subjects. Effect of beta-2 agonist therapy.
European journal of clinical investigation 22, 732-739 [PubMed:1335872]
[show Abstract]
Leukotriene B4 levels were measured after stimulation by calcium ionophore A23187: (i) in peripheral, neutrophils (PMN) from allergic asthmatics, rhinitis and healthy subjects; (ii) in macrophages collected by bronchoalveolar lavage. LTB4 levels in PMNs were significantly higher in non-treated allergic asthmatics and non-treated subjects with rhinitis compared to controls. Beta-2 agonist-treated asthmatics showed a significantly decreased LTB4 production which was not different from those of controls. In vitro, LTB4 production decreased significantly after PMN incubation with Salbutamol (10(-6) mol l-1). LTB4 produced by AM collected by BAL was measured in non-treated (n = 5) and treated (n = 11) asthmatics with inhaled beta-2 agonist. AM collected from all controls and non-treated asthmatics produced LTB4. By contrast, no production of LTB4 was observed in the treated group. LTB4 production decreased when normal AM were incubated in vitro with Salbutamol (10(-8) mol l-1). These results suggest that biochemical differences occur in PMN and macrophages from subjects treated with beta-2 agonist, presumably in changing the 5-lipoxygenase pathway. | Fogh J, Poulsen LK, Bisgaard H (1992)
A specific assay for leukotriene B4 in human whole blood.
Journal of pharmacological and toxicological methods 28, 185-190 [PubMed:1338371]
[show Abstract]
Leukotrienes (LTs) are potent mediators of inflammatory and allergic responses, and are present in biological fluids in minute amounts, that is, in the picogram range. The aim of this study was to develop and validate a method for determination of LTB4 synthesized in vitro in human whole blood. Heparinized blood was stimulated with calcium-ionophore A23187 at 37 degrees C. After 30 min cells were separated by centrifugation. LTB4 was analyzed by radioimmunoassay (RIA). When sample preparation was restricted to protein precipitation with acetone, interference was demonstrated by lack of parallelism between standard and sample dilution curves. Purification was, therefore, extended by combinations of the following steps: 1) protein precipitation, 2) lipid extractions, and 3) high-performance liquid chromatography (HPLC). One of two commercially available LTB4 standards was found to contain multiple components, several of which were immunoreactive in RIA. Even for the standard containing pure LTB4, interference was demonstrated by lack of parallelism between sample and standard dilution curves. Testing eight combinations of varying purification steps, we found that only a three-step purification procedure, including 1) solid-phase extraction, 2) protein precipitation at -20 degrees C, and 3) HPLC, was able to eliminate interference in RIA. Using this procedure, the recovery was 78%. Stimulation of whole blood from normal subjects with calcium-ionophore showed optimal LTB4 production at 10 microM ionophore, yielding 6.6 ng LTB4/mL blood. | Sieunarine K, Lawrence-Brown MM, Goodman MA, Prendergast FJ, Rocchetta S (1992)
Plasma levels of the lipid mediators, leukotriene B4 and lyso platelet-activating factor, in intraoperative salvaged blood.
Vox sanguinis 63, 168-171 [PubMed:1333134]
[show Abstract]
It has been shown that white cells and platelets release their granules into the plasma of salvaged blood. Whether this release is due to destruction alone or a combination of destruction and activation is not known. Lipid mediators, platelet-activating factor and leukotriene B4, are produced by activated white cells and platelets and have effects on the cardiovascular, respiratory and immune systems and the microcirculation. The aim was to determine if white cells and platelets are activated in salvaged blood by measuring the levels of these lipid mediators. Ten patients undergoing aortic surgery, where intraoperative salvage was used, were studied. Blood samples were taken from the patient's circulation and the salvaged blood before and after washing. The levels of leukotriene (LTB4) and lyso platelet-activating factor (PAF, the stable degradation product of PAF) were measured in the samples by a radioimmunoassay and a bioassay, respectively. The levels of both these substances increased in the unwashed salvaged blood (mean patient levels: LTB4 27 +/- 4.3 ng/ml and L-PAF 73 +/- 8.5 ng/ml; mean unwashed blood levels: LTB4 95 +/- 12.2 ng/ml and L-PAF 172.9 +/- 26.4 ng/ml) and were reduced by washing of the collected blood (mean washed blood levels of LTB4, 23.9 +/- 4.8 ng/ml, and L-PAF 18 +/- 5 ng/ml). The increase of the lipid mediators in the unwashed salvaged blood indicates that white cells and platelets are activated and releasing lipid mediators. Washing of the collected blood is effective in removing the lipid mediators. | Blackburn WD, Heck LW, Loose LD, Eskra JD, Carty TJ (1991)
Inhibition of 5-lipoxygenase product formation and polymorphonuclear cell degranulation by tenidap sodium in patients with rheumatoid arthritis.
Arthritis and rheumatism 34, 204-210 [PubMed:1847289]
[show Abstract]
We studied the effect of tenidap sodium, a new antiinflammatory/antirheumatic drug (120 mg/day for 7 days), on eicosanoid production and neutrophil degranulation in patients with rheumatoid arthritis. Endogenous prostaglandin E2 levels and ex vivo production of leukotriene B4 (LTB4) were measured in synovial fluid samples obtained at baseline and 1 week later. We measured peripheral blood polymorphonuclear cell (PMN) degranulation following surface-bound IgG stimulation, a possible 5-lipoxygenase product-mediated event, by determining lactoferrin and elastase release into the culture fluid. We found decreased levels of endogenous prostaglandin E2 as measured by radioimmunoassay, and decreased ex vivo production of LTB4 by PMN as measured by high performance liquid chromatography, in synovial fluid samples from patients who took tenidap. Release of the granule proteins lactoferrin and elastase was decreased in PMN obtained from patients receiving tenidap, as well as in the PMN incubated in vitro with tenidap. Improvement in clinical measures paralleled the biochemical changes. The unique 5-lipoxygenase inhibitory property of tenidap, as measured by LTB4 production and degranulation, suggests that it may have clinical activity which differentiates it from nonsteroidal antiinflammatory drugs. | Ahmadzadeh N, Shingu M, Nobunaga M, Tawara T (1991)
Relationship between leukotriene B4 and immunological parameters in rheumatoid synovial fluids.
Inflammation 15, 497-503 [PubMed:1661709]
[show Abstract]
Leukotriene B4 (LTB4) was measured in synovial fluid from 20 patients with rheumatoid arthritis and 15 patients with osteoarthritis. The level of LTB4 was significantly higher in synovial fluid from rheumatoid arthritis patients as compared with synovial fluid from osteoarthritis patients. LTB4 levels also significantly correlated with cell numbers, rheumatoid factor, and immune complexes in synovial fluid from rheumatoid arthritis patients. There was an inverse correlation between LTB4 levels and complement components. The high-pressure liquid chromatography peak of immunoreactivity extracted from the synovial fluid occurred at a retention volume identical to that of authentic LTB4. These results suggest that the increased level of this mediator in synovial fluid may contribute to perpetuation of inflammation and tissue destruction in rheumatoid arthritis. | Ford-Hutchinson AW (1981)
Leukotriene B4 and neutrophil function: a review.
Journal of the Royal Society of Medicine 74, 831-833 [PubMed:6271967] |
|
2011-03-17
