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Chemical Compound Review

LEUKOTRIENE B4     (5S,6Z,8E,10E,12R,14Z)-5,12- dihydroxyicosa...

Synonyms: LEUKOTRIENE_B4, LTB4, CHEMBL65061, BSPBio_001364, CHEBI:15647, ...
 
 
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Disease relevance of LEUKOTRIENE B4

 

Psychiatry related information on LEUKOTRIENE B4

  • Moreover, judging from the time-response characteristics, this priming for LTB4 release could be inhibited in the later stages of pretreatment, when the O2(-)-releasing capacity was enhanced [6].
  • In the present study we have demonstrated a reduction of the pain threshold in humans after intracutaneous deposition of LTB4 [7].
 

High impact information on LEUKOTRIENE B4

  • Measurements of leukotriene B4 (LTB4) production suggest that this risk is mediated through upregulation of the leukotriene pathway [8].
  • Furthermore, CHO cells expressing exogenous BLTR showed marked chemotactic responses towards low concentrations of LTB4 in a pertussis-toxin-sensitive manner [9].
  • LTB4 can also bind and activate the intranudear transcription factor PPAR alpha, resulting in the activation of genes that terminate inflammatory processes [9].
  • LTB4 elicited BLT1-dependent chemotaxis in effector cells, but not in naive or central memory cells [10].
  • Here we report that activated mast cells induced chemotaxis of effector, but not central memory, CD8+ T cells through production of leukotriene B4 (LTB4) [11].
 

Chemical compound and disease context of LEUKOTRIENE B4

 

Biological context of LEUKOTRIENE B4

 

Anatomical context of LEUKOTRIENE B4

  • These studies indicate that LTB4 production by activated peripheral leukocytes could be important for the recruitment of effector CD8+ T cells to sites of inflammation [11].
  • Human peripheral blood PMNs exposed to PGE2 (as in exudates) switched eicosanoid biosynthesis from predominantly LTB4 and 5-lipoxygenase (5-LO)-initiated pathways to LXA4, a 15-LO product that "stopped" PMN infiltration [22].
  • BLT1 mediated LTB4-induced T helper type 1 (T(H)1) and T(H)2 cell chemotaxis and firm adhesion to endothelial cells under flow, as well as early CD4+ and CD8+ T cell recruitment into the airway in an asthma model [23].
  • Leukotriene B4 (LTB4) was originally described as a potent lipid myeloid cell chemoattractant, rapidly generated from innate immune cells, that activates leukocytes through the G protein-coupled receptor BLT1 [23].
  • In this paper we have described the binding of nanomoler concentrations of [3H]leukotriene B4 (LTB4) to human polymorphonuclear leukocytes [24].
 

Associations of LEUKOTRIENE B4 with other chemical compounds

  • This study demonstrates the levels of both lipoxins and leukotrienes (LTC4, LTD4, LTB4, and omega-oxidized LTB4) generated from endogenous sources of arachidonate by PMN primed with recombinant human granulocyte/macrophage colony-stimulating factor and in coincubations with platelets (1:1 to 1:100 ratio) [25].
  • T. gondii-induced inhibition of LTB4 release by calcium ionophore A23187-stimulated monocyte-derived macrophage is reversed by interferon (IFN)-gamma treatment of the monolayers [26].
  • These results also unveil a dual role for red blood cells in upregulating LTB4 biosynthesis, namely, the removal of endogenous Ado and the conversion of LTA4 released by activated PMNs [27].
  • In the cells from ETrA-fed rats, LTB4 synthesis was inhibited relative to control values, but synthesis of the other products of 5-lipoxygenase metabolism, 5-hydroxyeicosatetraenoic acid (5-HETE) and the all-trans isomers of LTB4, were not inhibited [28].
  • Furthermore, pretreatment of cells with actinomycin D or cycloheximide inhibited not only the induction of lipid body formation by PAF, but also the PAF-induced "priming" for enhanced PGE2 and LTB4 in PMN [29].
  • Repertaxin reduced LTB4 production in joint tissue, and neutrophil recruitment induced by CXCL1 or CXCL5 was inhibited by MK886, suggesting a sequential mechanism [30].
 

Gene context of LEUKOTRIENE B4

  • Leukotriene (LT) A(4) hydrolase/aminopeptidase (LTA4H) is a bifunctional zinc enzyme that catalyzes the biosynthesis of LTB4, a potent lipid chemoattractant involved in inflammation, immune responses, host defense against infection, and PAF-induced shock [31].
  • Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function [32].
  • Administration of sulindac (320 ppm) to Min/+ mice reduced the tumor number by 95% but did not alter the levels of PGE2 and LTB4 in intestinal tissues [33].
  • The order of efficacy was formyl-met-leu-phe > C5a > > LTB4 > interleukin 8 > platelet-activating factor [34].
  • Isolation of the m-BLTR gene will form the basis of future experiments to elucidate the selective role of LTB4, as opposed to cysteinyl-leukotrienes, in murine models of inflammation [35].
 

Analytical, diagnostic and therapeutic context of LEUKOTRIENE B4

  • LTB4 induced extensive damage to the cellular membranes and cytoplasmic contents of the organisms as observed by transmission electron microscopy [26].
  • Quantities of LTB4 in cell-free supernatants of AM stimulated with LPS were determined by reverse-phase high-performance liquid chromatography and corresponded well with results obtained by radioimmunoassay [36].
  • This correlated with blockade of LTB4 production as measured by high performance liquid chromatography using freshly isolated alveolar macrophages, as well as blockade of [3H]LTB4 production by macrophages prelabeled with [3H]arachidonate [20].
  • The formation of [3H]inositol tris-phosphate (IP3) by [3H]inositol-labeled neutrophils stimulated by LTB4 decreased by 71% after 3 wk (0.033 +/- 0.013% [3H] release, mean +/- SEM) and by 90% after 10 wk (0.011 +/- 0.011%) from predict values (0.114 +/- 0.030%) as quantitated by beta-scintillation counting after resolution on HPLC [37].
  • Oral administration of 0.8 g DHA/kg did not increase DHA or eicosapentaenoic acid in the PMN phospholipid fraction and did not decrease LTB4 production by PMN at 6 h after administration [38].

References

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  2. Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes. Goldman, D.W., Chang, F.H., Gifford, L.A., Goetzl, E.J., Bourne, H.R. J. Exp. Med. (1985) [Pubmed]
  3. Inhibition of leukotriene B4-receptor interaction suppresses eosinophil infiltration and disease pathology in a murine model of experimental allergic encephalomyelitis. Gladue, R.P., Carroll, L.A., Milici, A.J., Scampoli, D.N., Stukenbrok, H.A., Pettipher, E.R., Salter, E.D., Contillo, L., Showell, H.J. J. Exp. Med. (1996) [Pubmed]
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  11. Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4. Ott, V.L., Cambier, J.C., Kappler, J., Marrack, P., Swanson, B.J. Nat. Immunol. (2003) [Pubmed]
  12. Impaired superoxide anion, platelet-activating factor, and leukotriene B4 synthesis by neutrophils in cirrhosis. Laffi, G., Carloni, V., Baldi, E., Rossi, M.E., Azzari, C., Gresele, P., Marra, F., Gentilini, P. Gastroenterology (1993) [Pubmed]
  13. The role of leukotriene B4 in Clostridium difficile toxin A-induced ileitis in rats. McVey, D.C., Vigna, S.R. Gastroenterology (2005) [Pubmed]
  14. Prostaglandin E2 limits arachidonic acid availability and inhibits leukotriene B4 synthesis in rat alveolar macrophages by a nonphospholipase A2 mechanism. Christman, B.W., Christman, J.W., Dworski, R., Blair, I.A., Prakash, C. J. Immunol. (1993) [Pubmed]
  15. IgE-dependent and ionophore-induced generation of leukotrienes by dog mastocytoma cells. Phillips, M.J., Gold, W.M., Goetzl, E.J. J. Immunol. (1983) [Pubmed]
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  18. In vitro and in vivo effects of leukotriene B4 antagonism in a primate model of asthma. Turner, C.R., Breslow, R., Conklyn, M.J., Andresen, C.J., Patterson, D.K., Lopez-Anaya, A., Owens, B., Lee, P., Watson, J.W., Showell, H.J. J. Clin. Invest. (1996) [Pubmed]
  19. Neutrophil-mediated changes in vascular permeability are inhibited by topical application of aspirin-triggered 15-epi-lipoxin A4 and novel lipoxin B4 stable analogues. Takano, T., Clish, C.B., Gronert, K., Petasis, N., Serhan, C.N. J. Clin. Invest. (1998) [Pubmed]
  20. Relative contribution of leukotriene B4 to the neutrophil chemotactic activity produced by the resident human alveolar macrophage. Martin, T.R., Raugi, G., Merritt, T.L., Henderson, W.R. J. Clin. Invest. (1987) [Pubmed]
  21. Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4. Goodwin, J.S., Atluru, D., Sierakowski, S., Lianos, E.A. J. Clin. Invest. (1986) [Pubmed]
  22. Lipid mediator class switching during acute inflammation: signals in resolution. Levy, B.D., Clish, C.B., Schmidt, B., Gronert, K., Serhan, C.N. Nat. Immunol. (2001) [Pubmed]
  23. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Tager, A.M., Bromley, S.K., Medoff, B.D., Islam, S.A., Bercury, S.D., Friedrich, E.B., Carafone, A.D., Gerszten, R.E., Luster, A.D. Nat. Immunol. (2003) [Pubmed]
  24. Specific binding of leukotriene B4 to a receptor on human polymorphonuclear leukocytes. Kreisle, R.A., Parker, C.W. J. Exp. Med. (1983) [Pubmed]
  25. Formation of lipoxins and leukotrienes during receptor-mediated interactions of human platelets and recombinant human granulocyte/macrophage colony-stimulating factor-primed neutrophils. Fiore, S., Serhan, C.N. J. Exp. Med. (1990) [Pubmed]
  26. Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity. Yong, E.C., Chi, E.Y., Henderson, W.R. J. Exp. Med. (1994) [Pubmed]
  27. Suppression of leukotriene B4 biosynthesis by endogenous adenosine in ligand-activated human neutrophils. Krump, E., Picard, S., Mancini, J., Borgeat, P. J. Exp. Med. (1997) [Pubmed]
  28. Effect of dietary supplementation with n-9 eicosatrienoic acid on leukotriene B4 synthesis in rats: a novel approach to inhibition of eicosanoid synthesis. James, M.J., Gibson, R.A., Neumann, M.A., Cleland, L.G. J. Exp. Med. (1993) [Pubmed]
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  30. CXCR2-specific chemokines mediate leukotriene B4-dependent recruitment of neutrophils to inflamed joints in mice with antigen-induced arthritis. Grespan, R., Fukada, S.Y., Lemos, H.P., Vieira, S.M., Napimoga, M.H., Teixeira, M.M., Fraser, A.R., Liew, F.Y., McInnes, I.B., Cunha, F.Q. Arthritis Rheum. (2008) [Pubmed]
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  38. Intravenous infusion of tridocosahexaenoyl-glycerol emulsion into rabbits. Effects on leukotriene B4/5 production and fatty acid composition of plasma and leukocytes. Nakamura, N., Hamazaki, T., Yamazaki, K., Taki, H., Kobayashi, M., Yazawa, K., Ibuki, F. J. Clin. Invest. (1993) [Pubmed]
 
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