Nitric oxide inhibits superoxide production by inflammatory polymorphonuclear leukocytes

Abstract

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 ([Formula: see text]) produced by polymorphonuclear leukocytes (PMNs) accumulated in the inflamed area. We injected phosphate-buffered saline (control group), 6 μmol ofl- N 5-(1-iminoethyl)ornithine (l-NIO group), or 6 μmol ofl-arginine (l-arginine group) into the granuloma pouch induced by carrageenan in rats.[Formula: see text] plus[Formula: see text] (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 thel-arginine group ( P < 0.05). When PMNs from treated rats were incubated in vitro, the production of superoxide anion ([Formula: see text]) decreased by ∼46% in thel-arginine group. Furthermore,[Formula: see text] was inhibited in PMNs whenl-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[Formula: see text] production for cell-mediated injury.