Differential mechanisms of intracellular killing of Mycobacterium avium and Listeria monocytogenes by activated human and murine macrophages. The role of nitric oxide.
Murine peritoneal macrophages activated with interferon-gamma (IFN-gamma) produce large quantities of nitric oxide and are efficient in the killing of certain intracellular pathogens. To examine the role of this mechanism in the killing of Mycobacterium avium by murine and human macrophages, we infected mouse peritoneal macrophages and human monocyte-derived macrophages with M. avium and Listeria monocytogenes and stimulated the cells with recombinant tumour necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) or IFN-gamma, in the presence or absence of N-monomethyl-L-arginine (NMA) or arginase. Neither competitive inhibition with NMA nor depletion of arginine by arginase had any effect on the inhibition of growth/intracellular killing of M. avium by activated human and murine macrophages. In contrast, activation of murine but not human macrophages infected with L. monocytogenes by IFN-gamma was significantly inhibited by the addition of NMA/arginase. Furthermore, murine macrophages produced large concentrations of nitric oxide following stimulation with recombinant cytokines, although no significant increase of nitric oxide production was observed with human monocyte-derived macrophages.
Bermudez
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Kuzell Institute for Arthritis and Infectious Diseases, Medical Research Institute of San Francisco, California Pacific Medical Centre 94115.
D000818:Animals; D001119:Arginase / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D009162:Mycobacterium avium / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D001119:Arginase