Disease relevance of leukotriene-C4

• The results indicate that enhanced production of leukotriene C4 is a common feature of murine autoimmunity and suggest further that aberrations in 5-lipoxygenase activity may play a role in the development of lupus [1].
• The major AA metabolites that were synthesized by the granuloma macrophages were shown to be leukotriene C4 and mono-hydroxyeicosatetraenoic acids [2].
• Our previous studies have shown that the development of ischemic necrosis was not due to thrombus formation, but to release of vasoconstricting mediators from the intestinal tissue, such as leukotriene C4 [3].
• In vivo production of leukotriene B4 and leukotriene C4 in rabbit colitis. Relationship to inflammation [4].
• It is concluded that systemic anaphylaxis in the guinea pig is associated with endogenous generation of leukotriene C4 (up to 1 nmol/kg during a 30-min period after the challenge [5].

High impact information on leukotriene-C4

• Epidermal growth factor activates calcium channels by phospholipase A2/5-lipoxygenase-mediated leukotriene C4 production [6].
• We conclude that PLA2/5-lipoxygenase-mediated leukotriene C4 production constitutes a novel and specific signal transduction pathway in growth factor action [6].
• We report that: EGF-induced Ca2+ channel activity is eliminated by lipoxygenase inhibition and is mimicked by artificial induction of lipoxygenase activity; addition of leukotriene C4 can fully mimic EGF in its ability to activate Ca2+ channels; and EGF induces a rapid accumulation of intracellular leukotriene C4 [6].
• IgE-dependent release of leukotriene C4 from alveolar macrophages [7].
• The cocultured eosinophils became hypodense and generated about three times as much leukotriene C4 upon activation with calcium ionophore and killed about three times as many antibody-coated larvae of Schistosoma mansoni as freshly isolated normodense eosinophils [8].

Chemical compound and disease context of leukotriene-C4

• Both Listeria peritoneal macrophages and blood monocytes produce equal or greater quantities of thromboxane A2 relative to prostaglandins I2 and E2 or leukotriene C4 whereas resident cells produce 1/10 to 1/25 as much thromboxane A2 compared to the other products [9].
• A high affinity binding site for leukotriene C4 (LTC4), one component of slow reacting substance of anaphylaxis, has been identified in a membrane preparation from rat lung [10].
• 5,8,11-Eicosatriynoic acid, a lipoxygenase inhibitor, prevented the biosynthesis of leukotriene C4 (ID50, 5 microM) by mastocytoma cells [11].
• Mouse mastocytoma cells incubated with ionophore A23187 and eicosapentaenoic acid (n-3) produced a slow reacting substance with different properties compared with leukotriene C4 (previously designated leukotriene C) [12].
• Bile acid perfusion stimulated PGE2, leukotriene C4, and DNA release in all groups studied, but leukotriene C4 release was significantly higher in Crohn's disease patients [13].

Biological context of leukotriene-C4

• However the release of leukotriene C4 was transient and could not account for the prolonged intestinal vasoconstriction [3].
• We found that chronic growth stimulation by leukotriene C4, a compound found in increased amounts in inflamed skin, induced pleiotropic modifications in the normal melanocyte phenotype [14].
• Leukotriene C4/D4 induces P-selectin and sialyl Lewis(x)-dependent alterations in leukocyte kinetics in vivo [15].
• During the period of its infusion, leukotriene C4 produced a significant elevation of mean arterial pressure and reductions in cardiac output and renal blood flow, as measured by electromagnetic flow probes [16].
• The immediate reduction of renal blood flow and glomerular filtration rate in response to intravenous infusion of leukotriene C4 in the rat prompted an analysis of isolated rat renal glomeruli for the presence of specific receptors for leukotriene C4 [17].

Anatomical context of leukotriene-C4

• The accumulation of leukotriene C4 in the choroid plexus was not dependent on tissue binding or metabolism of leukotriene C4 [18].
• In vitro experimentation using dispersed human lung mast cells demonstrated that azatadine base, a compound with known H1-antihistamine properties, inhibited anti-IgE-induced release of histamine and leukotriene C4 by 45% and 85%, respectively [19].
• The anaphylatoxin C5a is a potent trigger for basophil degranulations, but in contrast to IgE-dependent basophil activation, it does not result in the synthesis of sulfidoleukotrienes (leukotriene C4/D4/E4) [20].
• Aberrant production of leukotriene C4 by macrophages from autoimmune-prone mice [1].
• Oxidative degradation of leukotriene C4 by human monocytes and monocyte-derived macrophages [21].

Associations of leukotriene-C4 with other chemical compounds

• Consistent with this hypothesis, leukotriene C4 in vitro was transported into and released from isolated rabbit choroid plexus by a system that was specific, energy-dependent, probenecid-sensitive, and depressed by cold temperatures [18].
• Most importantly, IL-3 "primes" basophils to release large amounts of leukotriene C4 after challenge with C5a (mean of 50 gp LTC4 per nanograms cellular histamine), while neither peptide alone is capable of inducing the formation of bioactive lipids [20].
• A23187 greatly increased the amount of lipoxygenase products secreted from LPS-primed macrophages, leukotriene C4 synthesis being increased 150-fold [22].
• Eosinophil activation was initiated in vitro with 10(-6) M FMLP and 5 micrograms/ml cytochalasin B and was assessed by measurement of eosinophil peroxidase (EPO), leukotriene C4 (LTC4) and superoxide radical (.O2-) secretion [23].
• Eicosanoid production was also assayed by incubating colonic specimens and assaying the media for prostaglandin E2, leukotriene B4, and leukotriene C4 by radioimmunoassay [24].

Gene context of leukotriene-C4

• In this study we show that mature human basophils are capable of expressing IL-4 and examine the regulation of IL-4 production in comparison with the lipid mediator leukotriene C4 [25].
• Membrane vesicles prepared from ACNU-treated cells also displayed elevated transport activities for leukotriene C4, a known substrate for MRP [26].
• Multidrug resistance protein. Identification of regions required for active transport of leukotriene C4 [27].
• Extranuclear lipid bodies, elicited by CCR3-mediated signaling pathways, are the sites of chemokine-enhanced leukotriene C4 production in eosinophils and basophils [28].
• The neutralization of MCP-1 in allergic animals and instillation of MCP-1 in normal animals was related to leukotriene C4 levels in the bronchoalveolar lavage and was directly induced in pulmonary mast cells by MCP-1 [29].

Analytical, diagnostic and therapeutic context of leukotriene-C4

• Leukotriene C4- and D4-induced diffuse peripheral constriction of swine coronary artery accompanied by ST elevation on the electrocardiogram: angiographic analysis [30].
• Finally, using the indirect immunofluorescence technique, nerve endings in the median eminence and cell bodies in the preoptic area reacting with antibodies raised against leukotriene C4 were observed [31].
• Renal and systemic hemodynamic responses to intravenous infusion of leukotriene C4 in the rat [16].
• Extracts of media from log-phase cells were shown by high-pressure liquid chromatography to contain leukotriene C4, and synthesis of this compound was inhibited by ETYA, as judged by measurement of UV absorbance and radioactivity [32].
• In 20 patients undergoing craniotomy tissue specimens were immediately frozen after removal and tissue leukotriene C4 levels were determined by radioimmunoassay [33].

References