S-NITROSO-N-ACETYLPENICILLAMINE REDUCES LEUKOCYTE ADHESION TO TYPE-I COLLAGEN

The initial step in the migration of neutrophils to the extravascular space is adhesion to the endothelium. We examined the effect of nitric oxide on this process by treating human neutrophils with S-nitroso-N- acetylpenicillamine (SNAP), a NO-producing compound. Since NO has been shown to increase the level of cGMP in other cell types, we used 8-Br -cGMP in order to mimic the effects of NO. Indeed, both these treatmen ts resulted in a reduced adhesion of neutrophils to type I collagen co ated surfaces. After a prolonged incubation with SNAP, the adhesion wa s the same as for untreated cells. SNAP incubation reduced the F-actin content in the cells whereas 8-Br-cGMP increased it, demonstrating di fferent mechanisms of action on F-actin. These data suggest that endot helium-derived nitric oxide is an important endogenous modulator of ne utrophil adhesion, but the effect is not mediated by a cGMP-dependent regulation of F-actin levels.