Nitric oxide mediates the inhibition of neutrophil migration induced by systemic administration of LPS

To investigate the role of NO in the inhibition of neutrophil migration by circulating endotoxin, mice were pretreated with NO synthase inhibitors or with a free radical scavenger (D-penicillamine), before intravenous LPS inj ection. LPS dose-dependently inhibited the thioglycollate-induced neutrophi l migration into the peritoneal cavities. Aminoguanidine, a selective induc ible NO synthase inhibitor, abolished the inhibition of neutrophil migratio n and the increase in serum nitrate levels induced by a nonlethal dose of L PS. During lethal endotoxemia aminoguanidine partially abolished the neutro phil migration inhibition. Additionally, D-penicillamine prevented the inhi bition of neutrophil migration caused by LPS. However, Nitro-L-Arginine, a selective constitutive NO synthase inhibitor, did not prevent neutrophil mi gration inhibition. Aminoguanidine treatment did not affect the systemic in creased levels of TNF-alpha, IL-1 beta, and IL-10, suggesting that NO is th e final mediator involved in the inhibition of neutrophil migration. Our re sults suggest that NO released by the inducible NO synthase. mediates the i nhibition of neutrophil migration mediated by circulating LPS.