Ethanol-induced neutrophil apoptosis is mediated through nitric oxide

Clinical reports indicate that acute ethanol intoxication in chronic ethano l abusers is associated with neutropenia. We hypothesize that ethanol accel erates the apoptosis of neutrophils thus decreasing the peripheral blood co unt of neutrophils, We studied the effect of ethanol on neutrophil apoptosi s in vivo as well as in vitro. Human neutrophils harvested from healthy sub jects after an alcohol drinking binge showed enhanced apoptosis (before, 0. 5 +/- 0.25 vs, after, 26.1 +/- 2.6% apoptotic neutrophils/field). Peritonea l neutrophils isolated from ethanol-treated rats also showed increased (P < 0.0001) apoptosis when compared with neutrophils isolated from control rat s (control, 0.8 +/- 0.2% vs, ethanol, 11.8 +/- 0.7% apoptotic neutrophils/f ield), In in vitro studies, ethanol in concentrations of 50 mM and higher a ccelerated the apoptosis of human and rat neutrophils, This effect of ethan ol oil human neutrophils tvas time dependent. DNA isolated front ethanol-tr eated human neutrophils displayed integer multiples of 180 base pairs (ladd er pattern), further confirming the effect of ethanol on neutrophil apoptos is, N-G-monomethyl-L-arginine monoacetate and N-G-nitro-L-arginine methyl e ster, inhibitors of nitric oxide (NO) synthase, attenuated the ethanol-indu ced neutrophil apoptosis. Sodium nitroprusside, a NO donor, also promoted n eutrophil apoptosis, Moreover, ethanol enhanced neutrophil expression of in ducible NO synthase, In addition, ethanol stimulated neutrophil NO generati on These results suggest that ethanol accelerates neutrophil apoptosis. Thi s effect of ethanol on neutrophil apoptosis seems to be mediated through th e generation of NO.