Nitric oxide inhibits superoxide production by inflammatory polymorphonuclear leukocytes.
Nitric oxide (NO.) has a complex role in the inflammatory response. In this study, we modified the levels of endogenous NO. in vivo in an acute model of inflammation and evaluated the interactions between NO. and superoxide anion (O2-.) produced by polymorphonuclear leukocytes (PMNs) accumulated in the inflamed area. We injected phosphate-buffered saline (control group), 6 mumol of L-N5-(1-iminoethyl)ornithine (L-NIO group), or 6 mumol of L-arginine (L-arginine group) into the granuloma pouch induced by carrageenan in rats. NO2- plus NO3- (indicative of NO. generation) was 188 nmol in the exudate of the control group, but it decreased in the L-NIO group (P < 0.05) and increased in the L-arginine group (P < 0.05). When PMNs from treated rats were incubated in vitro, the production of superoxide anion (O2-.) decreased by approximately 46% in the L-arginine group. Furthermore, O2-. was inhibited in PMNs when L-arginine was added to the incubation medium before phorbol 12-myristate 13-acetate stimulation but not when added simultaneously. Our results suggest a protective role for NO. in inflammation, through the inactivation of NADPH oxidase and the consequent impairment of O2-. production for cell-mediated injury.
Ródenas
J
J
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.
Mitjavila
M T
MT
Carbonell
T
T
D000818:Animals; D005122:Exudates and Transudates / Q000378:metabolism; D005609:Free Radicals; D007249:Inflammation / Q000097:blood*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005609:Free Radicals; D013481:Superoxides; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009952:Ornithine; D013755:Tetradecanoylphorbol Acetate