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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].


  1. The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate. Schröder, J.M. J. Exp. Med. (1989) [Pubmed]
  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]
  4. 5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in Brown Norway rats. Stamatiou, P., Hamid, Q., Taha, R., Yu, W., Issekutz, T.B., Rokach, J., Khanapure, S.P., Powell, W.S. J. Clin. Invest. (1998) [Pubmed]
  5. Impaired ex vivo leukotriene B4 production characterizes the metabolic syndrome and is improved after weight reduction. Tsai, I.J., Beilin, L.J., Puddey, I.B., Croft, K.D., Barden, A. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  6. Lipopolysaccharide primes human alveolar macrophages for enhanced release of superoxide anion and leukotriene B4: self-limitations of the priming response with protein synthesis. Suzuki, K., Yamamoto, T., Sato, A., Murayama, T., Amitani, R., Yamamoto, K., Kuze, F. Am. J. Respir. Cell Mol. Biol. (1993) [Pubmed]
  7. Leukotriene B4 produces hyperalgesia in humans. Bisgaard, H., Kristensen, J.K. Prostaglandins (1985) [Pubmed]
  8. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Helgadottir, A., Manolescu, A., Helgason, A., Thorleifsson, G., Thorsteinsdottir, U., Gudbjartsson, D.F., Gretarsdottir, S., Magnusson, K.P., Gudmundsson, G., Hicks, A., Jonsson, T., Grant, S.F., Sainz, J., O'Brien, S.J., Sveinbjornsdottir, S., Valdimarsson, E.M., Matthiasson, S.E., Levey, A.I., Abramson, J.L., Reilly, M.P., Vaccarino, V., Wolfe, M.L., Gudnason, V., Quyyumi, A.A., Topol, E.J., Rader, D.J., Thorgeirsson, G., Gulcher, J.R., Hakonarson, H., Kong, A., Stefansson, K. Nat. Genet. (2006) [Pubmed]
  9. A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., Shimizu, T. Nature (1997) [Pubmed]
  10. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Goodarzi, K., Goodarzi, M., Tager, A.M., Luster, A.D., von Andrian, U.H. Nat. Immunol. (2003) [Pubmed]
  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]
  16. Assessment of leukotriene B4 synthesis in human lymphocytes by using high performance liquid chromatography and radioimmunoassay methods. Poubelle, P.E., Borgeat, P., Rola-Pleszczynski, M. J. Immunol. (1987) [Pubmed]
  17. Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response. Goldman, D.W., Goetzl, E.J. J. Exp. Med. (1984) [Pubmed]
  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]
  29. Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids. Bozza, P.T., Payne, J.L., Goulet, J.L., Weller, P.F. J. Exp. Med. (1996) [Pubmed]
  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]
  31. Crystal structure of human leukotriene A(4) hydrolase, a bifunctional enzyme in inflammation. Thunnissen, M.M., Nordlund, P., Haeggström, J.Z. Nat. Struct. Biol. (2001) [Pubmed]
  32. 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. Del Prete, A., Shao, W.H., Mitola, S., Santoro, G., Sozzani, S., Haribabu, B. Blood (2007) [Pubmed]
  33. Sulindac causes rapid regression of preexisting tumors in Min/+ mice independent of prostaglandin biosynthesis. Chiu, C.H., McEntee, M.F., Whelan, J. Cancer Res. (1997) [Pubmed]
  34. Characterization of two different forms of mitogen-activated protein kinase kinase induced in polymorphonuclear leukocytes following stimulation by N-formylmethionyl-leucyl-phenylalanine or granulocyte-macrophage colony-stimulating factor. Thompson, H.L., Marshall, C.J., Saklatvala, J. J. Biol. Chem. (1994) [Pubmed]
  35. Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B4 receptor-transfected cells. Martin, V., Ronde, P., Unett, D., Wong, A., Hoffman, T.L., Edinger, A.L., Doms, R.W., Funk, C.D. J. Biol. Chem. (1999) [Pubmed]
  36. Macrophages cultured in vitro release leukotriene B4 and neutrophil attractant/activation protein (interleukin 8) sequentially in response to stimulation with lipopolysaccharide and zymosan. Rankin, J.A., Sylvester, I., Smith, S., Yoshimura, T., Leonard, E.J. J. Clin. Invest. (1990) [Pubmed]
  37. Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. Sperling, R.I., Benincaso, A.I., Knoell, C.T., Larkin, J.K., Austen, K.F., Robinson, D.R. J. Clin. Invest. (1993) [Pubmed]
  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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