title: Reciprocal effects of interleukin-4 and interferon-gamma on immunoglobulin E-mediated mast cell degranulation: a role for nitric oxide but not peroxynitrite or cyclic guanosine monophosphate.
abstract: We report that cultured rat peritoneal cells spontaneously synthesize nitric oxide and this is associated with active suppression of mast cell secretory function. Addition of interleukin-4 (IL-4) or the nitric oxide synthase inhibitor N-monomethyl-l-arginine to peritoneal cells inhibited nitric oxide synthesis and enhanced anti-IgE-mediated mast cell degranulation, measured as serotonin release. Interferon-gamma (IFN-gamma) completely overcame the enhancement of serotonin release and suppression of nitrite production induced by IL-4. Over several experiments, with or without IL-4 and/or IFN-gamma, serotonin release correlated inversely with nitrite production. On a cell-for-cell basis, non-mast cells produced approximately 30 times more nitrite than mast cells in peritoneal cell populations, with or without IFN-gamma stimulation. The nitric oxide donor S-nitrosoglutathione inhibited anti-IgE-induced serotonin release from purified mast cells, whereas 8-bromo-cyclic GMP, the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, superoxide dismutase and the peroxynitrite scavenger uric acid, were without effect. We conclude that IL-4 and IFN-gamma reciprocally regulate mast cell secretory responsiveness via control of nitric oxide synthesis by accessory cells; the nitric oxide effect on mast cells is direct but does not involve cyclic GMP or peroxynitrite.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, UK.
authors.forename: M L
authors.initials: ML
authors.lastname: Deschoolmeester
authors.forename: N C
authors.initials: NC
authors.lastname: Eastmond
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: I
authors.initials: I
authors.lastname: Kimber
authors.forename: D A
authors.initials: DA
authors.lastname: Basketter
authors.forename: J W
authors.initials: JW
authors.lastname: Coleman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015550:Cell Degranulation; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D051381:Rats; D011914:Rats, Inbred BN; D026422:S-Nitrosoglutathione; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D013268:Stimulation, Chemical; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009573:Nitrites; D009603:Nitroso Compounds; D015847:Interleukin-4; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; D007073:Immunoglobulin E; D026422:S-Nitrosoglutathione; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D005978:Glutathione