The involvement of nitric oxide in the anti-Candida albicans activity of rat neutrophils.
Rat peritoneal neutrophils (PMN) spontaneously release nitric oxide (NO) when incubated in vitro. Addition of the NO synthase inhibitor L-monomethylarginine (L-NMMA) to the PMN reduces NO production and impairs the killing of the yeast Candida albicans, both effects being reversed by L-arginine. These data strongly suggest that oxidative metabolism of L-arginine by PMN is involved in the candidacidal activity of these cells. Rat blood PMN, which do not produce significant amounts of NO, exhibit a reduced killing capacity compared with peritoneal cells, except when they are obtained from lipopolysaccharide (LPS)-treated rats. In this case they produce measurable amounts of nitrite and express high fungicidal activity in vitro. Confirming the candidacidal activity of NO, the exposure of the C. albicans cultures to different concentrations of NO donors leads to a reduction in their survival. The candidacidal activity related to the NO pathway in rat PMN is phagocytosis dependent, since the activity can be inhibited by cytochalasin B. However, the oxidative products of oxygen released by rat PMN do not seem to be involved in their candidacidal activity, as incubation of the cells with phorbol myristate acetate (PMA) increases release of superoxide anion but does not affect the pattern of killing. Our results suggest that NO could be an important candidacidal pathway in rat neutrophils.
Fierro
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Department of Pharmacology, 1B, Universidade do Estado do Rio de Janeiro, Brazil.
Barja-Fidalgo
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Cunha
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Ferreira
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D000818:Animals; D002176:Candida albicans / Q000254:growth & development*; D003571:Cytochalasin B / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008070:Lipopolysaccharides; D014665:Vasodilator Agents; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003571:Cytochalasin B; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D013755:Tetradecanoylphorbol Acetate