leukotriene c4

Summary

Summary: The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)

Top Publications

  1. Sjostrom M, Jakobsson P, Heimburger M, Palmblad J, Haeggstrom J. Human umbilical vein endothelial cells generate leukotriene C4 via microsomal glutathione S-transferase type 2 and express the CysLT(1) receptor. Eur J Biochem. 2001;268:2578-86 pubmed
    ..Moreover, HUVEC were found to express the CysLT1 receptor in line with a paracrine and autocrine role for cysteinyl-leukotrienes in endothelial cell function. ..
  2. Di Capite J, Nelson C, Bates G, Parekh A. Targeting Ca2+ release-activated Ca2+ channel channels and leukotriene receptors provides a novel combination strategy for treating nasal polyposis. J Allergy Clin Immunol. 2009;124:1014-21.e1-3 pubmed publisher
    ..Hence our results identify a new potential strategy for combating polyposis and mast cell-dependent allergies. ..
  3. Zhu Y, Bertics P. Chemoattractant-induced signaling via the Ras-ERK and PI3K-Akt networks, along with leukotriene C4 release, is dependent on the tyrosine kinase Lyn in IL-5- and IL-3-primed human blood eosinophils. J Immunol. 2011;186:516-26 pubmed publisher
  4. Chen Z, Hopper Borge E, Belinsky M, Shchaveleva I, Kotova E, Kruh G. Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003;63:351-8 pubmed
    ..The determination that MRP7 has the facility for mediating the transport of conjugates such as E(2)17betaG indicates that it is a lipophilic anion transporter involved in phase III (cellular extrusion) of detoxification. ..
  5. Payen L, Gao M, Westlake C, Theis A, Cole S, Deeley R. Functional interactions between nucleotide binding domains and leukotriene C4 binding sites of multidrug resistance protein 1 (ABCC1). Mol Pharmacol. 2005;67:1944-53 pubmed
  6. Saino H, Ukita Y, Ago H, Irikura D, Nisawa A, Ueno G, et al. The catalytic architecture of leukotriene C4 synthase with two arginine residues. J Biol Chem. 2011;286:16392-401 pubmed publisher
    ..In this study enzymatic assay with mutant enzymes demonstrates that Arg-104 is required for the binding and activation of GSH and that Arg-31 is needed for catalysis probably by activating the epoxide group of LTA(4). ..
  7. Hashizume K, Black K. Increased endothelial vesicular transport correlates with increased blood-tumor barrier permeability induced by bradykinin and leukotriene C4. J Neuropathol Exp Neurol. 2002;61:725-35 pubmed
    Bradykinin and leukotriene C4 (LTC4) have been shown to increase molecular transport across the blood-tumor barrier (BTB)...
  8. Thompson C, Cloutier A, Bosse Y, Poisson C, Larivee P, McDonald P, et al. Signaling by the cysteinyl-leukotriene receptor 2. Involvement in chemokine gene transcription. J Biol Chem. 2008;283:1974-84 pubmed
    ..These findings suggest the potential implication of CysLT2 in the inflammatory response through the modulation of chemokine gene transcription. ..
  9. Bandeira Melo C, Sugiyama K, Woods L, Phoofolo M, Center D, Cruikshank W, et al. IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4- and autocrine CCR3-chemokine-mediated signaling. J Immunol. 2002;168:4756-63 pubmed
  10. Hattori Y, Ohno T, Ae T, Saeki T, Arai K, Mizuguchi S, et al. Gastric mucosal protection against ethanol by EP2 and EP4 signaling through the inhibition of leukotriene C4 production. Am J Physiol Gastrointest Liver Physiol. 2008;294:G80-7 pubmed
    ..The present results indicate that EP(2) and EP(4) receptor signaling inhibits ethanol-induced gastric mucosal injury through cancellation of collecting venule constriction by reducing LTC(4) production. ..

Detail Information

Publications62

  1. Sjostrom M, Jakobsson P, Heimburger M, Palmblad J, Haeggstrom J. Human umbilical vein endothelial cells generate leukotriene C4 via microsomal glutathione S-transferase type 2 and express the CysLT(1) receptor. Eur J Biochem. 2001;268:2578-86 pubmed
    ..Moreover, HUVEC were found to express the CysLT1 receptor in line with a paracrine and autocrine role for cysteinyl-leukotrienes in endothelial cell function. ..
  2. Di Capite J, Nelson C, Bates G, Parekh A. Targeting Ca2+ release-activated Ca2+ channel channels and leukotriene receptors provides a novel combination strategy for treating nasal polyposis. J Allergy Clin Immunol. 2009;124:1014-21.e1-3 pubmed publisher
    ..Hence our results identify a new potential strategy for combating polyposis and mast cell-dependent allergies. ..
  3. Zhu Y, Bertics P. Chemoattractant-induced signaling via the Ras-ERK and PI3K-Akt networks, along with leukotriene C4 release, is dependent on the tyrosine kinase Lyn in IL-5- and IL-3-primed human blood eosinophils. J Immunol. 2011;186:516-26 pubmed publisher
  4. Chen Z, Hopper Borge E, Belinsky M, Shchaveleva I, Kotova E, Kruh G. Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol Pharmacol. 2003;63:351-8 pubmed
    ..The determination that MRP7 has the facility for mediating the transport of conjugates such as E(2)17betaG indicates that it is a lipophilic anion transporter involved in phase III (cellular extrusion) of detoxification. ..
  5. Payen L, Gao M, Westlake C, Theis A, Cole S, Deeley R. Functional interactions between nucleotide binding domains and leukotriene C4 binding sites of multidrug resistance protein 1 (ABCC1). Mol Pharmacol. 2005;67:1944-53 pubmed
  6. Saino H, Ukita Y, Ago H, Irikura D, Nisawa A, Ueno G, et al. The catalytic architecture of leukotriene C4 synthase with two arginine residues. J Biol Chem. 2011;286:16392-401 pubmed publisher
    ..In this study enzymatic assay with mutant enzymes demonstrates that Arg-104 is required for the binding and activation of GSH and that Arg-31 is needed for catalysis probably by activating the epoxide group of LTA(4). ..
  7. Hashizume K, Black K. Increased endothelial vesicular transport correlates with increased blood-tumor barrier permeability induced by bradykinin and leukotriene C4. J Neuropathol Exp Neurol. 2002;61:725-35 pubmed
    Bradykinin and leukotriene C4 (LTC4) have been shown to increase molecular transport across the blood-tumor barrier (BTB)...
  8. Thompson C, Cloutier A, Bosse Y, Poisson C, Larivee P, McDonald P, et al. Signaling by the cysteinyl-leukotriene receptor 2. Involvement in chemokine gene transcription. J Biol Chem. 2008;283:1974-84 pubmed
    ..These findings suggest the potential implication of CysLT2 in the inflammatory response through the modulation of chemokine gene transcription. ..
  9. Bandeira Melo C, Sugiyama K, Woods L, Phoofolo M, Center D, Cruikshank W, et al. IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4- and autocrine CCR3-chemokine-mediated signaling. J Immunol. 2002;168:4756-63 pubmed
  10. Hattori Y, Ohno T, Ae T, Saeki T, Arai K, Mizuguchi S, et al. Gastric mucosal protection against ethanol by EP2 and EP4 signaling through the inhibition of leukotriene C4 production. Am J Physiol Gastrointest Liver Physiol. 2008;294:G80-7 pubmed
    ..The present results indicate that EP(2) and EP(4) receptor signaling inhibits ethanol-induced gastric mucosal injury through cancellation of collecting venule constriction by reducing LTC(4) production. ..
  11. Tabas L, Dantzig A. A high-throughput assay for measurement of multidrug resistance protein-mediated transport of leukotriene C4 into membrane vesicles. Anal Biochem. 2002;310:61-6 pubmed
    ..The microtiter dish assay is a more expedient method for measuring transport into membrane vesicles and will have applications to other transporters. ..
  12. Chen Z, Guo Y, Belinsky M, Kotova E, Kruh G. Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol Pharmacol. 2005;67:545-57 pubmed
    ..uptake of a range of physiological and synthetic lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone ..
  13. Hirata H, Arima M, Fukushima Y, Sugiyama K, Tokuhisa T, Fukuda T. Leukotriene C4 aggravates bleomycin-induced pulmonary fibrosis in mice. Respirology. 2013;18:674-81 pubmed publisher
    ..Recent reports have suggested that leukotriene C4 (LTC4 ) is an important regulator of pulmonary fibrosis...
  14. Di Capite J, Ng S, Parekh A. Decoding of cytoplasmic Ca(2+) oscillations through the spatial signature drives gene expression. Curr Biol. 2009;19:853-8 pubmed publisher
    ..Furthermore, we show that the spatial profile of a Ca(2+) oscillation provides a novel mechanism whereby a pleiotropic messenger specifically activates gene expression. ..
  15. Yang S, Huang X, Chen H, Xu D, Chen L, Kong Y, et al. Increased leukotriene c4 synthesis accompanied enhanced leukotriene c4 synthase expression and activities of ischemia-reperfusion-injured liver in rats. J Surg Res. 2007;140:36-44 pubmed
    ..leukotrienes (LTs), the first committed synthesis step of which is that LTC4 synthesis enzymes including leukotriene C4 synthase (LTC4S), microsomal glutathione-S-transferase (mGST)2, and mGST3-catalyzed LTA4 and reduced ..
  16. Perng D, Wu Y, Chang K, Wu M, Chiou Y, Su K, et al. Leukotriene C4 induces TGF-beta1 production in airway epithelium via p38 kinase pathway. Am J Respir Cell Mol Biol. 2006;34:101-7 pubmed
    ..Early intervention to stop these processes may be useful in preventing airway fibrosis in chronic allergic inflammation. ..
  17. Farias S, Frey L, Murphy R, Heidenreich K. Injury-related production of cysteinyl leukotrienes contributes to brain damage following experimental traumatic brain injury. J Neurotrauma. 2009;26:1977-86 pubmed publisher
  18. Yang R, Cui L, Hou Y, Riordan J, Chang X. ATP binding to the first nucleotide binding domain of multidrug resistance-associated protein plays a regulatory role at low nucleotide concentration, whereas ATP hydrolysis at the second plays a dominant role in ATP-dependent leukotriene C4 transpor. J Biol Chem. 2003;278:30764-71 pubmed
  19. Dannull J, Schneider T, Lee W, de Rosa N, Tyler D, Pruitt S. Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function. Blood. 2012;119:3113-22 pubmed publisher
    ..Collectively, our data suggest that LTC(4) represents a promising candidate to replace PGE(2) in DC maturation protocols for cancer vaccination. ..
  20. Belinsky M, Chen Z, Shchaveleva I, Zeng H, Kruh G. Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002;62:6172-7 pubmed
    ..These results indicate that MRP6 is a glutathione conjugate pump that is able to confer low levels of resistance to certain anticancer agents. ..
  21. Serio K, Luo C, Luo L, Mao J. TNF-alpha downregulates the leukotriene C4 synthase gene in mononuclear phagocytes. Am J Physiol Lung Cell Mol Physiol. 2007;292:L215-22 pubmed
    ..We conclude that TNF-alpha exposure downregulates the synthetic capacity for cysteinyl LT release and LTC(4) synthase gene expression in monocytes/macrophages via a transcriptional mechanism. ..
  22. Qian Y, Qiu W, Gao M, Westlake C, Cole S, Deeley R. Characterization of binding of leukotriene C4 by human multidrug resistance protein 1: evidence of differential interactions with NH2- and COOH-proximal halves of the protein. J Biol Chem. 2001;276:38636-44 pubmed
  23. Zaitsu M, Hamasaki Y, Aoki Y, Miyazaki S. A novel pharmacologic action of glucocorticosteroids on leukotriene C4 catabolism. J Allergy Clin Immunol. 2001;108:122-4 pubmed
    ..The activation of gamma-GTPRE might be regulated transcriptionally. This is a novel regulatory mechanism by which glucocorticosteroids exert antiasthma activities. ..
  24. Ma K, Zhang Y, Zhu D, Lou Y. Protective effects of asiatic acid against D-galactosamine/lipopolysaccharide-induced hepatotoxicity in hepatocytes and kupffer cells co-cultured system via redox-regulated leukotriene C4 synthase expression pathway. Eur J Pharmacol. 2009;603:98-107 pubmed publisher
    ..Taken together, asiatic acid can protect against D-GalN/LPS-induced hepatotoxicity partly via redox-regulated LTC(4)S expression pathway. ..
  25. Feng C, Beller E, Bagga S, Boyce J. Human mast cells express multiple EP receptors for prostaglandin E2 that differentially modulate activation responses. Blood. 2006;107:3243-50 pubmed
    ..extracellular signal-regulated kinase (ERK), exocytosis, and production of prostaglandin D2 (PGD2), as well as leukotriene C4 (LTC4) when protein kinase A (PKA) was inhibited...
  26. Chang W, Parekh A. Close functional coupling between Ca2+ release-activated Ca2+ channels, arachidonic acid release, and leukotriene C4 secretion. J Biol Chem. 2004;279:29994-9 pubmed
    ..by Ca2+ entering through CRAC channels is used to synthesize the potent paracrine proinflammatory signal leukotriene C4 (LTC4)...
  27. Rossi A, Acquaviva A, Iuliano F, Di Paola R, Cuzzocrea S, Sautebin L. Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-{gamma}. J Leukoc Biol. 2005;78:985-91 pubmed
    ..Thus, the balance between COX and 5-LO metabolites could be of great importance in controlling macrophage functions and consequently, inflammation and tumor promotion. ..
  28. Sharma R, Singhal S, Wickramarachchi D, Awasthi Y, Awasthi S. RLIP76 (RALBP1)-mediated transport of leukotriene C4 (LTC4) in cancer cells: implications in drug resistance. Int J Cancer. 2004;112:934-42 pubmed
    ..These results suggest that RLIP76 is the major LTC(4) transporter in cancer cells and that its transport activity is regulated by PKC-alpha-mediated phosphorylation. ..
  29. Becher U, Ghanem A, Tiyerili V, Furst D, Nickenig G, Mueller C. Inhibition of leukotriene C4 action reduces oxidative stress and apoptosis in cardiomyocytes and impedes remodeling after myocardial injury. J Mol Cell Cardiol. 2011;50:570-7 pubmed publisher
    ..Inhibition of leukotriene C(4) reduces levels of oxidative stress and apoptosis and demonstrates beneficial effects on myocardial remodeling after left ventricular injury. ..
  30. Zaitsu M, Hamasaki Y, Tsuji K, Matsuo M, Fujita I, Aoki Y, et al. Dexamethasone accelerates catabolism of leukotriene C4 in bronchial epithelial cells. Eur Respir J. 2003;22:35-42 pubmed
    ..transpeptidase-related enzyme in human bronchial epithelial cells, which accelerates inactivation of leukotriene C4 via conversion to leukotriene E4...
  31. Oyoshi M, He R, Kanaoka Y, Elkhal A, Kawamoto S, Lewis C, et al. Eosinophil-derived leukotriene C4 signals via type 2 cysteinyl leukotriene receptor to promote skin fibrosis in a mouse model of atopic dermatitis. Proc Natl Acad Sci U S A. 2012;109:4992-7 pubmed publisher
    ..Strategies that block eosinophil infiltration, cys-LT production, or the CysLT(2)R might be useful in the treatment of AD. ..
  32. Hong F, Yang S. Ischemic preconditioning decreased leukotriene C4 formation by depressing leukotriene C4 synthase expression and activity during hepatic I/R injury in rats. J Surg Res. 2012;178:1015-21 pubmed publisher
    ..They suggest that the beneficial effects of IP may be involved in repression of LTC4 generation during hepatic I/R injury. ..
  33. Zhang X, Gonzalez Cobos J, Schindl R, Muik M, Ruhle B, Motiani R, et al. Mechanisms of STIM1 activation of store-independent leukotriene C4-regulated Ca2+ channels. Mol Cell Biol. 2013;33:3715-23 pubmed publisher
    ..These store-independent Orai3/Orai1 channels are gated by cytosolic leukotriene C4 (LTC4) and require STIM1 downstream LTC4 action...
  34. Long E, Hellberg K, Foncea R, Hertzel A, Suttles J, Bernlohr D. Fatty acids induce leukotriene C4 synthesis in macrophages in a fatty acid binding protein-dependent manner. Biochim Biophys Acta. 2013;1831:1199-207 pubmed
    ..Activated macrophages produce a variety of pro-inflammatory lipids such as leukotriene C4 (LTC4) and 5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE) suggesting the hypothesis that fatty acids may ..
  35. Tancowny B, Karpov V, Schleimer R, Kulka M. Substance P primes lipoteichoic acid- and Pam3CysSerLys4-mediated activation of human mast cells by up-regulating Toll-like receptor 2. Immunology. 2010;131:220-30 pubmed publisher
    ..Pretreatment of LAD2 with SP followed by stimulation with Pam3CSK4 or LTA increased production of leukotriene C4 (LTC(4) ) and interleukin (IL)-8 compared with treatment with Pam3CSK4 or LTA alone (>2-fold; P<0ยท01)...
  36. Chavez J, Young H, Corry D, Lieberman M. Interactions between leukotriene C4 and interleukin 13 signaling pathways in a mouse model of airway disease. Arch Pathol Lab Med. 2006;130:440-6 pubmed
    During an asthmatic episode, leukotriene C4 (LTC4) and interleukin 13 (IL-13) are released into the airways and are thought to be central mediators of the asthmatic response...
  37. Di Capite J, Shirley A, Nelson C, Bates G, Parekh A. Intercellular Ca2+ wave propagation involving positive feedback between CRAC channels and cysteinyl leukotrienes. FASEB J. 2009;23:894-905 pubmed publisher
    ..We conclude that a positive-feedback cascade involving CRAC channels and cysteinyl leukotrienes constitute a novel mechanism for sustaining mast cell activation. ..
  38. Maekawa A, Kanaoka Y, Xing W, Austen K. Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors. Proc Natl Acad Sci U S A. 2008;105:16695-700 pubmed publisher
    ..Our findings establish the existence of a third receptor, CysLT(E)R, that responds preferentially to LTE(4), the most abundant cys-LT in biologic fluids, and thus reveal a new target for therapeutic intervention. ..
  39. Gulliksson M, Palmberg L, Nilsson G, Ahlstedt S, Kumlin M. Release of prostaglandin D2 and leukotriene C4 in response to hyperosmolar stimulation of mast cells. Allergy. 2006;61:1473-9 pubmed
    ..In contrast, there was a correlation between release of PGD(2) and LTC(4), following immunological stimulation. The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation. ..
  40. Kamohara M, Takasaki J, Matsumoto M, Matsumoto Si -, Saito T, Soga T, et al. Functional characterization of cysteinyl leukotriene CysLT(2) receptor on human coronary artery smooth muscle cells. Biochem Biophys Res Commun. 2001;287:1088-92 pubmed
    ..Additionally, these cells showed chemotactic responses to LTC(4). This is the first report on the physiological role of CysLT(2), and the findings suggest that CysLT(2) has biological significance in the cardiovascular system. ..
  41. Vieira de Abreu A, Assis E, Gomes G, Castro Faria Neto H, Weller P, Bandeira Melo C, et al. Allergic challenge-elicited lipid bodies compartmentalize in vivo leukotriene C4 synthesis within eosinophils. Am J Respir Cell Mol Biol. 2005;33:254-61 pubmed
    ..Such in vivo allergen-driven lipid bodies function as intracellular compartments of LTC(4) synthesis. ..
  42. Christmas P, Weber B, McKee M, Brown D, Soberman R. Membrane localization and topology of leukotriene C4 synthase. J Biol Chem. 2002;277:28902-8 pubmed
    ..The differential localization of two very similar integral membrane proteins suggests that mechanisms other than size-dependent exclusion regulate their passage to the inner nuclear membrane. ..
  43. Chibana K, Ishii Y, Asakura T, Fukuda T. Up-regulation of cysteinyl leukotriene 1 receptor by IL-13 enables human lung fibroblasts to respond to leukotriene C4 and produce eotaxin. J Immunol. 2003;170:4290-5 pubmed
    ..In the Th2 cytokine-rich milieu, such as that in bronchial asthma, CysLT1R expression on fibroblasts might be up-regulated, thereby allowing CysLTs to act effectively and increase eosinophilic inflammation. ..
  44. Chen Y, Bieneman A, Creticos P, Chichester K, Schroeder J. IFN-alpha inhibits IL-3 priming of human basophil cytokine secretion but not leukotriene C4 and histamine release. J Allergy Clin Immunol. 2003;112:944-50 pubmed
    ..in the presence and absence of IL-3 priming before stimulating through the IgE receptor to release histamine, leukotriene C4, and IL-4. Effects of IFN-alpha on IL-3-mediated IL-13 secretion and basophil survival were also tested...
  45. Lie W, Homburg C, Kuijpers T, Knol E, Mul F, Roos D, et al. Regulation and kinetics of platelet-activating factor and leukotriene C4 synthesis by activated human basophils. Clin Exp Allergy. 2003;33:1125-34 pubmed
    ..This study provides a first comprehensive comparison of PAF and LTC4 synthesis in highly purified human basophils, stimulated with a variety of stimuli. ..
  46. Devakumar A, O Dell D, Walker J, Reilly J. Structural analysis of leukotriene C4 isomers using collisional activation and 157 nm photodissociation. J Am Soc Mass Spectrom. 2008;19:14-26 pubmed
    The fragmentation of 5-hydroxy-6-glutathionyl-7,9,11,14-eicosatetraenoic acid [leukotriene C4 or LTC4 (5, 6)] and its isomeric counterpart LTC4 (14, 15) were studied by low and high-energy collisional induced dissociation (CID) and 157 nm ..
  47. Mueller C, Wassmann K, Widder J, Wassmann S, Chen C, Keuler B, et al. Multidrug resistance protein-1 affects oxidative stress, endothelial dysfunction, and atherogenesis via leukotriene C4 export. Circulation. 2008;117:2912-8 pubmed publisher
    ..These findings indicate that MRP1 and LTC(4) exert proatherosclerotic effects and that both MRP1 and LTC(4) are potentially promising targets for atheroprotective therapy. ..
  48. Gonzalez Cobos J, Zhang X, Zhang W, Ruhle B, Motiani R, Schindl R, et al. Store-independent Orai1/3 channels activated by intracrine leukotriene C4: role in neointimal hyperplasia. Circ Res. 2013;112:1013-25 pubmed publisher
    ..Orai3 and Orai3-containing channels provide novel targets for control of VSMC remodeling during vascular injury or disease. ..
  49. Wu P, Oleschuk C, Mao Q, Keller B, Deeley R, Cole S. Analysis of human multidrug resistance protein 1 (ABCC1) by matrix-assisted laser desorption ionization/time of flight mass spectrometry: toward identification of leukotriene C4 binding sites. Mol Pharmacol. 2005;68:1455-65 pubmed
    ..The intrinsically photoreactive glutathione-conjugated cysteinyl leukotriene C4 (LTC4) is a high-affinity physiological substrate of MRP1 and is widely regarded as a model compound for ..
  50. Bandeira Melo C, Hall J, Penrose J, Weller P. Cysteinyl leukotrienes induce IL-4 release from cord blood-derived human eosinophils. J Allergy Clin Immunol. 2002;109:975-9 pubmed
  51. Kim S, Lu Y, Kwon O, Hwangbo K, Seo C, Lee S, et al. Manassantin A isolated from Saururus chinensis inhibits 5-lipoxygenase-dependent leukotriene C4 generation by blocking mitogen-activated protein kinase activation in mast cells. Biol Pharm Bull. 2011;34:1769-72 pubmed
    ..Taken together, the present study suggests the Man A represents a potential therapeutic approach for the treatment of airway allergic-inflammatory diseases. ..
  52. Oliveira S, Hogaboam C, Berlin A, Lukacs N. SCF-induced airway hyperreactivity is dependent on leukotriene production. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1242-9 pubmed
    ..Altogether, these studies indicate that SCF-induced airway hyperreactivity is dependent upon leukotriene-mediated pathways. ..
  53. Jedlitschky G, Keppler D. Transport of leukotriene C4 and structurally related conjugates. Vitam Horm. 2002;64:153-84 pubmed
    Transport proteins control the release of the endogenous glutathione conjugate leukotriene C4 (LTC4) from leukotriene-synthesizing cells as well as its hepatobiliary and renal elimination...
  54. Nagy E, Andersson D, Caidahl K, Eriksson M, Eriksson P, Franco Cereceda A, et al. Upregulation of the 5-lipoxygenase pathway in human aortic valves correlates with severity of stenosis and leads to leukotriene-induced effects on valvular myofibroblasts. Circulation. 2011;123:1316-25 pubmed publisher
  55. Kitahata Y, Nunomura S, Terui T, Ra C. Prolonged culture of mast cells with high-glucose medium enhances the Fc epsilon RI-mediated degranulation response and leukotriene C4 production. Int Arch Allergy Immunol. 2010;152 Suppl 1:22-31 pubmed publisher
    ..Moreover, it is suggested that increased phosphorylation of cPLA(2) at the Ser505 residue contributes to the enhancement of LTC(4) secretion. ..
  56. Inoue T, Suzuki Y, Ra C. Epigallocatechin-3-gallate inhibits mast cell degranulation, leukotriene C4 secretion, and calcium influx via mitochondrial calcium dysfunction. Free Radic Biol Med. 2010;49:632-40 pubmed publisher
    ..These events may lead to [Ca(2+)](m) dysfunction and impair mitochondria-mediated facilitation of SOCE, thereby attenuating mast cell activation. ..
  57. Oskeritzian C, Zhao W, Min H, Xia H, Pozez A, Kiev J, et al. Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell. J Allergy Clin Immunol. 2005;115:1162-8 pubmed
    ..MC(T) and MC(TC) types of human mast cells (MCs) are distinguished from one another on the basis of the protease compositions of their secretory granules, but their functional and developmental relationships have been uncertain...
  58. Mesquita Santos F, Vieira de Abreu A, Calheiros A, Figueiredo I, Castro Faria Neto H, Weller P, et al. Cutting edge: prostaglandin D2 enhances leukotriene C4 synthesis by eosinophils during allergic inflammation: synergistic in vivo role of endogenous eotaxin. J Immunol. 2006;176:1326-30 pubmed
    ..regulate eosinophil trafficking, we asked whether PGD2 was also able to activate eosinophils and control their leukotriene C4 (LTC4)-synthesizing machinery...
  59. Dahlen S. Treatment of asthma with antileukotrienes: first line or last resort therapy?. Eur J Pharmacol. 2006;533:40-56 pubmed
    ..Further research needs and new areas for leukotriene involvement in respiratory diseases are also discussed. ..
  60. Chang W, Nelson C, Parekh A. Ca2+ influx through CRAC channels activates cytosolic phospholipase A2, leukotriene C4 secretion, and expression of c-fos through ERK-dependent and -independent pathways in mast cells. FASEB J. 2006;20:2381-3 pubmed
    ..Arachidonic acid can then be metabolized by the 5-lipoxygenase enzyme to generate the proinflammatory signal leukotriene C4 (LTC4)...
  61. Nuutinen P, Harvima I, Ackermann L. Histamine, but not leukotriene C4, is an essential mediator in cold urticaria wheals. Acta Derm Venereol. 2007;87:9-13 pubmed
    In addition to histamine, leukotriene C4 (LTC4) might also play a role in mediating cold urticaria wheals. To study the significance of LTC4 vs...
  62. Reddanna P, Prabhu K, Whelan J, Reddy C. Carboxypeptidase A-catalyzed direct conversion of leukotriene C4 to leukotriene F4. Arch Biochem Biophys. 2003;413:158-63 pubmed