Open AccessCytokine-treated human neutrophils contain inducible nitric oxide synthase that produces nitration of ingested bacteria.
Author(s) -
Thomas J. Evans,
Lee D.K. Buttery,
Adam Carpenter,
David R. Springall,
Julia M. Polak,
Jonathan Cohen
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.18.9553
Subject(s) - peroxynitrite , nitric oxide synthase , myeloperoxidase , nitric oxide , superoxide , chemistry , nitrotyrosine , biochemistry , tumor necrosis factor alpha , enzyme , cytokine , microbiology and biotechnology , biology , inflammation , immunology , organic chemistry
Although the production of NO within rodent phagocytes is well-characterized, its production and function within human phagocytes are less clear. We show here that neutrophils within human buffy coat preparations stimulated with a mixture of interleukin 1, tumor necrosis factor alpha, and interferon gamma contain inducible NO synthase mRNA and protein, one of the enzymes responsible for NO production. The protein colocalizes with myeloperoxidase within neutrophil primary granules. Using an inhibitor of NO synthase, L-N-monomethyl arginine, we show that activity of this enzyme is required for the formation of nitrotyrosine around phagocytosed bacteria, most likely through the intermediate production of peroxynitrite, a reaction product of NO and superoxide anions.