AN INCREASE IN NITRIC-OXIDE PRODUCED BY RAT PERITONEAL NEUTROPHILS ISNOT INVOLVED IN CELL APOPTOSIS

POLYMORPHONUCLEAR neutrophils (PMN) obtained from carrageenin-stimulat ed peritoneal cavities of rats, but not blood PMN, spontaneously produ ced nitric oxide (NO) when incubated in vitro. Incubation of the cells with the NO synthase inhibitors, L-imino-ethyl-L-ornithine (L-NIO) or N-G-monomethyl-L-arginine (L-NMMA), inhibited NO production. This inh ibition could be reversed by L-arginine. Incubation of PMN with lipopo lysaccharide (LPS) failed to enhance NO production. Pretreatment of th e rats with dexamethasone (DEXA) prior to carrageenin injection or inc ubation of PMN with the glucocorticoid in vitro partially inhibited th e spontaneous release of NO. On the other hand, when PMN obtained from DEXA pretreated rats were incubated in vitro with DEXA, NO synthase a ctivity and hence NO generation were almost abolished. A similar inhib ition was also observed following the addition of L-NIO or cycloheximi de to cultures of carrageenin-elicited PMN. The NO production by PMN d id not appear to be related to cell viability or apoptosis. Indeed, ne ither the blockade of NO generation by L-NIO nor the incubation of the neutrophils with a NO donor, S-nitroso-acetyl-penicillamine (SNAP) mo dified the pattern of LDH release or DNA fragmentation. In summary, it appears that PMN migration triggers a continuous NO synthesis, and th at NO produced by these cells is not related to their apoptosis.