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Phenotypic variation in mast cell responsiveness to the inhibitory action of nitric oxide
R D Koranteng1, R J Dearman, I Kimber
1Department of Pharmacology and Therapeutics, University of Liverpool, United Kingdom.
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 C1.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-gamma (IFN-gamma)-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-gamma to mouse peritoneal cells led to nitric oxide synthesis and this was associated with decreased IgE-mediated mast cell degranulation. IFN-gamma did not induce nitric oxide production by CMMC and degranulation of CMMC was not inhibited by nitric oxide generated by co-cultured IFN-gamma-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.