CYTOKINE-TREATED HUMAN NEUTROPHILS CONTAIN INDUCIBLE NITRIC-OXIDE SYNTHASE THAT PRODUCES NITRATION OF INGESTED BACTERIA

Although the production of NO within rodent phagocytes is well-charact erized, its production and function within human phagocytes are less c lear. We show here that neutrophils within human buffy coat preparatio ns stimulated with a mixture of interleukin 1, tumor necrosis factor a lpha, and interferon gamma contain inducible NO synthase mRNA and prot ein, one of the enzymes responsible for NO production, The protein col ocalizes with myeloperoxidase within neutrophil primary granules. Usin g an inhibitor of NO synthase, L-N-monomethyl arginine, we show that a ctivity of this enzyme is required for the formation of nitrotyrosine around phagocytosed bacteria, most likely through the intermediate pro duction of peroxynitrite, a reaction product of NO and superoxide anio ns.