OXYGEN-DEPENDENT INHIBITION OF NEUTROPHIL RESPIRATORY BURST BY NITRIC-OXIDE

Effect of nitric oxide (NO) on the respiratory burst of neutrophils wa s examined under different oxygen tensions. Phorbol myristate acetate (PMA) stimulated oxygen consumption and superoxide (O-2(-)) generation in neutrophils by a mechanism which was inhibited reversibly by NO. T he inhibitory effect of NO increased significantly with a decrease in oxygen tension in the medium. The inhibitory effect oi NO was suppress ed in medium containing oxyhemoglobin (HbO(2)), a NO scavenging agent. In contrast, 3-morpholinosydnonimine (SIN-1), a compound that rapidly generates peroxynitrite (ONOO-) from the released NO and O-2(-), slig htly stimulated the PMA-induced respiratory burst. These results sugge sted that NO, but not ONOO-, might reversibly inhibit superoxide gener ation by neutrophils especially at physiologically low oxygen tensions thereby decreasing oxygen toxicity particularly in and around hypoxic tissues.