The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Leukotriene C     (5S,6R,7E,9E,11Z,14Z)-6-[2- [(4-amino-4...

Synonyms: leukotriene C4, LTC4, BML1-E07, LS-72363, LTC (sub 4), ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Leukotriene C


Psychiatry related information on Leukotriene C


High impact information on Leukotriene C

  • We describe the functional activation (calcium mobilization) of this receptor by LTD4 and LTC4, and competition for radiolabelled LTD4 binding to this receptor by the cysteinyl leukotrienes and three structurally distinct classes of CysLT1-receptor antagonists [7].
  • KL at concentrations of 10 ng/ml elicited half-maximal eicosanoid generation and at concentrations of > 50 ng/ml elicited a maximal generation of approximately 15 ng LTC4 and 1 ng PGD2 per 10(6) cells, with 20% net beta-hexosaminidase release 10 min after stimulation [8].
  • However, after incubation with viable T. gondii, normal and chronic granulomatous disease monocytes release only the cyclooxygenase products TXB2 and PGE2 and fail to form LTB4, LTC4, or other 5-lipoxygenase products [9].
  • Freshly isolated, 2-h adherent human monocytes release both cyclooxygenase (e.g., thromboxane [TX] B2, prostaglandin [PG] E2) and 5-lipoxygenase (e.g., leukotriene [LT] B4, LTC4) products of arachidonic acid metabolism after stimulation by the calcium ionophore A23187 or ingestion of opsonized zymosan particles or heat-killed T. gondii [9].
  • Upon exposure to receptor-mediated stimuli (FMLP and thrombin), the levels of lipoxins generated were within the range of both LTB4 and LTC4 [10].

Chemical compound and disease context of Leukotriene C


Biological context of Leukotriene C

  • The initial vasoconstriction after PAF injection was due to a transient release of LTC4 since FPL 55712 pretreatment abolished the vasoconstriction [16].
  • Dose-dependent (1-100 nM) stimulation of [3H]thymidine incorporation, an index of cell proliferation, was observed in cells incubated with the sulfidopeptide LTs, LTC4 and LTD4, but not with LTB4 [17].
  • IL-4 inhibited the priming for increased IgE-dependent PGD2 and LTC4 production to the level obtained by activation of BMMCs maintained in IL-3 alone with an IC50 of approximately 0.2 ng/ml [18].
  • As measured by saturation experiments, the Kd and density of LTC4 binding sites in fraction I were 4.8 +/- 1.6 nM and 16.5 +/- 1.9 pmol/mg of protein, respectively, and in fraction IV were 4.7 +/- 1.5 nM and 81.4 +/- 19 pmol/mg of protein, respectively [19].
  • To define saturability and kinetics of LTC4 export, eosinophils were interacted with leukotriene A4 (LTA4) at 37 degrees C, and the methanolic extracts of the cell-associated and extracellular compartments were then analyzed for LTC4 content by reverse phase high performance liquid chromatography with on-line monitoring of absorbance at 280 nm [20].

Anatomical context of Leukotriene C

  • In addition, the cultured eosinophils generated approximately 2.5-fold more LTC4 than freshly isolated cells when stimulated with the calcium ionophore A23187 and manifested sevenfold greater antibody-dependent killing of S. mansoni larvae than the freshly isolated, normodense cells from the same donor [21].
  • The release of three preformed mediators and of LTC4 after fixation of IgE, washing of the sensitized cells, and antigen challenge unequivocally indicates a bone marrow-derived mast cell origin for these products [22].
  • The oxidative degradation of LTC4 is a capacity shared by neutrophils, eosinophils, and mononuclear phagocytes, and may be an important mechanism for the modulation of leukotriene activity in inflammatory lesions [5].
  • A preincubation of the basophils with IL-3 is strictly required for C5a-induced LTC4 synthesis, but not for an enhancement of degranulation [3].
  • Dynamics of leukotriene C production by macrophages [23].

Associations of Leukotriene C with other chemical compounds


Gene context of Leukotriene C

  • Interestingly, upon prolonged culture, a late phase of continuous LTC4 production is observed, which also requires two signals (IL-3 and C5a), but rather depends on their continuous presence than on their sequence of action [25].
  • A mutant form of MRP1, which transports LTC4 but not E(2)17betaG, also did not transport NNAL-O-glucuronide suggesting a commonality in the binding elements for these two glucuronidated substrates, despite their lack of reciprocal transport inhibition [26].
  • In this study, we investigated the physiological location of microsomal GST-II as well as the relative importance of this enzyme versus LTC4 synthase for the production of LTC4 in various human tissues and cells that have been previously demonstrated to possess LTC4 synthase activity [27].
  • Thus, depending on the presence of IL-3, GM-CSF, or IL-5, PAF is a potent basophil agonist capable of inducing histamine release as well as de novo synthesis of LTC4 [28].
  • Because the ATP-dependent export system has been implicated in the release of leukotriene C4 (LTC4), we examined the roles of P-gp and MRP in the release of LTC4 from normal murine mast cells (MC-9) [29].

Analytical, diagnostic and therapeutic context of Leukotriene C

  • High-performance liquid chromatography revealed the presence of leukotrienes C, D, and E, suggesting that nasal cells or fluids had the ability to degrade leukotriene C enzymatically [30].
  • As assessed by HPLC, LTC4 composed greater than 85% of the C-6 peptide leukotriene released at any skin site, whereas little LTD4 or LTE4 was detected [31].
  • Enhanced baseline cys-LT levels in bronchoalveolar lavage (BAL) fluid of AIA patients correlated uniquely with bronchial counts of LTC4 synthase+ cells (rho = 0.83, P = 0.01) [32].
  • Since intradermal injection of LTC4 in humans induces wheal and flare responses that persist for hours, our findings support the hypothesis that LTC4 is an important mediator of human allergic skin reactions [31].
  • The identification of the reaction product as LTC4 was confirmed by its identical retention time on reverse-phase HPLC to that of synthetic LTC4, the incorporation of [3H]glutathione into the product, its reactivity in a radioimmunoassay, and its UV absorption spectrum [33].


  1. Bronchoconstrictor effects of leukotriene C in humans. Weiss, J.W., Drazen, J.M., Coles, N., McFadden, E.R., Weller, P.F., Corey, E.J., Lewis, R.A., Austen, K.F. Science (1982) [Pubmed]
  2. Prevention of endogenous leukotriene production during anaphylaxis in the guinea pig by an inhibitor of leukotriene biosynthesis (MK-886) but not by dexamethasone. Guhlmann, A., Keppler, A., Kästner, S., Krieter, H., Brückner, U.B., Messmer, K., Keppler, D. J. Exp. Med. (1989) [Pubmed]
  3. Interleukin 3-dependent mediator release in basophils triggered by C5a. Kurimoto, Y., de Weck, A.L., Dahinden, C.A. J. Exp. Med. (1989) [Pubmed]
  4. The importance of leukotrienes in airway inflammation in a mouse model of asthma. Henderson, W.R., Lewis, D.B., Albert, R.K., Zhang, Y., Lamm, W.J., Chiang, G.K., Jones, F., Eriksen, P., Tien, Y.T., Jonas, M., Chi, E.Y. J. Exp. Med. (1996) [Pubmed]
  5. Oxidative degradation of leukotriene C4 by human monocytes and monocyte-derived macrophages. Neill, M.A., Henderson, W.R., Klebanoff, S.J. J. Exp. Med. (1985) [Pubmed]
  6. Behavioral and physiological effects of leukotriene C4. Landauer, M.R., Davis, H.D., Walden, T.L. Prostaglandins Leukot. Essent. Fatty Acids (1990) [Pubmed]
  7. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Lynch, K.R., O'Neill, G.P., Liu, Q., Im, D.S., Sawyer, N., Metters, K.M., Coulombe, N., Abramovitz, M., Figueroa, D.J., Zeng, Z., Connolly, B.M., Bai, C., Austin, C.P., Chateauneuf, A., Stocco, R., Greig, G.M., Kargman, S., Hooks, S.B., Hosfield, E., Williams, D.L., Ford-Hutchinson, A.W., Caskey, C.T., Evans, J.F. Nature (1999) [Pubmed]
  8. The immediate phase of c-kit ligand stimulation of mouse bone marrow-derived mast cells elicits rapid leukotriene C4 generation through posttranslational activation of cytosolic phospholipase A2 and 5-lipoxygenase. Murakami, M., Austen, K.F., Arm, J.P. J. Exp. Med. (1995) [Pubmed]
  9. 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]
  10. 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]
  11. Leukotrienes in the pathophysiology of kwashiorkor. Mayatepek, E., Becker, K., Gana, L., Hoffmann, G.F., Leichsenring, M. Lancet (1993) [Pubmed]
  12. Leukotriene C4 binding to rat lung membranes. Pong, S.S., DeHaven, R.N., Kuehl, F.A., Egan, R.W. J. Biol. Chem. (1983) [Pubmed]
  13. Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport. Loe, D.W., Almquist, K.C., Deeley, R.G., Cole, S.P. J. Biol. Chem. (1996) [Pubmed]
  14. Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. Penrose, J.F., Spector, J., Baldasaro, M., Xu, K., Boyce, J., Arm, J.P., Austen, K.F., Lam, B.K. J. Biol. Chem. (1996) [Pubmed]
  15. In vitro release of prostaglandins and leukotrienes from synovial tissue, cartilage, and bone in degenerative joint diseases. Wittenberg, R.H., Willburger, R.E., Kleemeyer, K.S., Peskar, B.A. Arthritis Rheum. (1993) [Pubmed]
  16. Release of leukotriene C4 by isolated, perfused rat small intestine in response to platelet-activating factor. Hsueh, W., Gonzalez-Crussi, F., Arroyave, J.L. J. Clin. Invest. (1986) [Pubmed]
  17. Leukotriene C4 binds to human glomerular epithelial cells and promotes their proliferation in vitro. Baud, L., Sraer, J., Perez, J., Nivez, M.P., Ardaillou, R. J. Clin. Invest. (1985) [Pubmed]
  18. Interleukin 4 suppresses c-kit ligand-induced expression of cytosolic phospholipase A2 and prostaglandin endoperoxide synthase 2 and their roles in separate pathways of eicosanoid synthesis in mouse bone marrow-derived mast cells. Murakami, M., Penrose, J.F., Urade, Y., Austen, K.F., Arm, J.P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  19. Subcellular distribution of leukotriene C4 binding units in cultured bovine aortic endothelial cells. Chau, L.Y., Hoover, R.L., Austen, K.F., Lewis, R.A. J. Immunol. (1986) [Pubmed]
  20. The identification of a distinct export step following the biosynthesis of leukotriene C4 by human eosinophils. Lam, B.K., Owen, W.F., Austen, K.F., Soberman, R.J. J. Biol. Chem. (1989) [Pubmed]
  21. Regulation of human eosinophil viability, density, and function by granulocyte/macrophage colony-stimulating factor in the presence of 3T3 fibroblasts. Owen, W.F., Rothenberg, M.E., Silberstein, D.S., Gasson, J.C., Stevens, R.L., Austen, K.F., Soberman, R.J. J. Exp. Med. (1987) [Pubmed]
  22. IgE-mediated release of leukotriene C4, chondroitin sulfate E proteoglycan, beta-hexosaminidase, and histamine from cultured bone marrow-derived mouse mast cells. Razin, E., Mencia-Huerta, J.M., Stevens, R.L., Lewis, R.A., Liu, F.T., Corey, E., Austen, K.F. J. Exp. Med. (1983) [Pubmed]
  23. Dynamics of leukotriene C production by macrophages. Rouzer, C.A., Scott, W.A., Hamill, A.L., Cohn, Z.A. J. Exp. Med. (1980) [Pubmed]
  24. Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages. Rouzer, C.A., Scott, W.A., Hamill, A.L., Cohn, Z.A. J. Exp. Med. (1982) [Pubmed]
  25. IgE-independent interleukin-4 expression and induction of a late phase of leukotriene C4 formation in human blood basophils. Ochensberger, B., Rihs, S., Brunner, T., Dahinden, C.A. Blood (1995) [Pubmed]
  26. Transport of the beta -O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). Requirement for glutathione or a non-sulfur-containing analog. Leslie, E.M., Ito , K., Upadhyaya, P., Hecht, S.S., Deeley, R.G., Cole, S.P. J. Biol. Chem. (2001) [Pubmed]
  27. Production of leukotriene C4 in different human tissues is attributable to distinct membrane bound biosynthetic enzymes. Scoggan, K.A., Jakobsson, P.J., Ford-Hutchinson, A.W. J. Biol. Chem. (1997) [Pubmed]
  28. Platelet-activating factor induces mediator release by human basophils primed with IL-3, granulocyte-macrophage colony-stimulating factor, or IL-5. Brunner, T., de Weck, A.L., Dahinden, C.A. J. Immunol. (1991) [Pubmed]
  29. Leukotriene C4 secretion from normal murine mast cells by a probenecid-sensitive and multidrug resistance-associated protein-independent mechanism. Nguyen, T., Gupta, S. J. Immunol. (1997) [Pubmed]
  30. Peptide leukotriene release after antigen challenge in patients sensitive to ragweed. Creticos, P.S., Peters, S.P., Adkinson, N.F., Naclerio, R.M., Hayes, E.C., Norman, P.S., Lichtenstein, L.M. N. Engl. J. Med. (1984) [Pubmed]
  31. Accumulation of leukotriene C4 and histamine in human allergic skin reactions. Talbot, S.F., Atkins, P.C., Goetzl, E.J., Zweiman, B. J. Clin. Invest. (1985) [Pubmed]
  32. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. Cowburn, A.S., Sladek, K., Soja, J., Adamek, L., Nizankowska, E., Szczeklik, A., Lam, B.K., Penrose, J.F., Austen, F.K., Holgate, S.T., Sampson, A.P. J. Clin. Invest. (1998) [Pubmed]
  33. Isolation and characterization of leukotriene C4 synthetase of rat basophilic leukemia cells. Yoshimoto, T., Soberman, R.J., Lewis, R.A., Austen, K.F. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
WikiGenes - Universities