Phenotypic variation in mast cell responsiveness to the inhibitory action of nitric oxide

Objective and design: The aim of this study was to investigate the possible phenotypic variations between mast cells in terms of their responsiveness to the inhibitory actions of nitric oxide. Materials: Unfractionated mouse peritoneal cells, purified rat peritoneal mast cells, mouse bone marrow-derived mast cells of the Cl.MC/C57.1 line (cultured mouse mast cells, CMMC) and rat basophilic leukemia cells of the RBL-2H3 line were used. Methods: Mast cells were cultured with interferon-γ(IFN-γ)-stimulated mouse peritoneal cells as a source of nitric oxide, or with the nitric oxide donor S-nitrosoglutathione (SNOG). After 24 h culture, the mast cells were challenged with anti-IgE, antigen, or calcium ionophore A23187, and degranulation measured as release of [3H]serotonin. Results: Addition of IFN-γ to mouse peritoneal cells led to nitric oxide synthesis and this was associated with decreased IgE-mediated mast cell degranulation. IFN-γ did not induce nitric oxide production by CMMC and degranulation of CMMC was not inhibited by nitric oxide generated by co-cultured IFN-γ-activated peritoneal cells. The nitric oxide donor SNOG inhibited degranulation of purified rat peritoneal mast cells, but not RBL-2H3 cells, stimulated by either IgE cross-linking or calcium ionophore. Conclusions: The inhibitory effects of nitric oxide on mast cell degranulation are variable and selective for phenotype. Such phenotypic differences may reflect important variations in regulation of mast cell function.