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


METHODS
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.
Koranteng
R D
RD
Department of Pharmacology and Therapeutics, University of Liverpool, United Kingdom.
Dearman
R J
RJ
Kimber
I
I
Coleman
J W
JW
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009603:Nitroso Compounds / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN; D026422:S-Nitrosoglutathione; D012701:Serotonin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D009569:Nitric Oxide; D012701:Serotonin; D026422:S-Nitrosoglutathione; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C496316:Nos3 protein, rat; D005978:Glutathione