NITRIC-OXIDE INHIBITS SUPEROXIDE PRODUCTION BY INFLAMMATORY POLYMORPHONUCLEAR LEUKOCYTES

Nitric oxide (NO .) has a complex role in the inflammatory response. I n 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 leukocy tes (PMNs) accumulated in the inflamed area. We injected phosphate-buf fered saline (control group), 6 mu mol of L-N-5-(1-iminoethyl)ornithin e (LNIO group), or 6 mu mol of L-arginine (L-arginine group) into the granuloma pouch induced by carrageenan in rats. NO2- plus NO3- (indica tive of NO . generation) was 188 nmol in the exudate of the control gr oup, but it decreased in the L-NIO group (P < 0.05) and increased in t he L-arginine group (P < 0.05). When PMNs from treated rats were incub ated in vitro, the production of superoxide anion (O-2(-).) decreased by similar to 46% in the L-arginine group. Furthermore, O-2(-). was in hibited in PMNs when L-arginine was added to the incubation medium bef ore phorbol 12-myristate 13-acetate stimulation but not when added sim ultaneously. Our results suggest a protective role for NO . in inflamm ation, through the inactivation of NADPH oxidase and the consequent im pairment of O-2(-). production for cell-mediated injury.