Bm. Tavares-murta et al., Nitric oxide mediates the inhibition of neutrophil migration induced by systemic administration of LPS, INFLAMMATIO, 25(4), 2001, pp. 247-253
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.