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Reciprocal effects of interleukin‐4 and interferon‐γ on immunoglobulin E‐mediated mast cell degranulation: a role for nitric oxide but not peroxynitrite or cyclic guanosine monophosphate
Author(s) -
Matthew L. deSchoolmeester,
Nigel C. Eastmond,
Rebecca J. Dearman,
Ian Kimber,
David A. Basketter,
John W. Coleman
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00662.x
Subject(s) - peroxynitrite , degranulation , cyclic guanosine monophosphate , nitric oxide , guanosine , chemistry , antibody , immunology , biochemistry , medicine , enzyme , receptor , superoxide , organic chemistry
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‐γ (IFN‐γ) 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‐γ, serotonin release correlated inversely with nitrite production. On a cell‐for‐cell basis, non‐mast cells produced ≈30 times more nitrite than mast cells in peritoneal cell populations, with or without IFN‐γ 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 1 H ‐[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‐γ 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.