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Nitric oxide-mediated apoptosis in murine mastocytoma.

To investigate how the number of mast cells is controlled, we studied a murine mastocytoma cell line. Based on electron microscopic observation of nuclear condensation and electrophoretic evidence with DNA fragmentation, these mastocytoma wells were shown to undergo apoptosis. This apoptosis was dependent on the concentrations of serum and L-arginine and was enhanced by TNF-alpha. We confirmed that apoptosis was mediated by nitric oxide (NO) synthase; inducible NO synthase (iNOS) mRNA was strongly expressed in apoptotic cells, while an inhibitor of NOS, NG-monomethyl-L-arginine, and dexamethasone prevented apoptosis in addition to inhibiting iNOS mRNA expression. Our results suggest that iNOS expression is very important in regulating the proliferation of mast cells under pathological conditions.