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 (O-2(-).) produced by polymorphonuclear leukocytes (PMNs) accumulated in the inflamed area. We injected phosphate-buffered saline (control group), 6 mu mol of L-N-5-(1-iminoethyl)ornithine (LNIO group), or 6 mu mol 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 (O-2(-).) decreased by similar to 46% in the L-arginine group. Furthermore, O-2(-). 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 O-2(-). production for cell-mediated injury.