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Ethanol‐induced neutrophil apoptosis is mediated through nitric oxide
Author(s) -
Singhal Pravin C.,
Patel Puja,
Nàhàr Nilay,
Franki Nicholas,
Kapasi Aditi,
Reddy Krishna,
Shah Neena,
Nwakoby Izuchukwu E.,
Mehrotra Bhoomi
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.66.6.930
Subject(s) - nitric oxide , biology , apoptosis , neutrophile , ethanol , microbiology and biotechnology , immunology , biochemistry , inflammation , endocrinology
Clinical reports indicate that acute ethanol intoxication in chronic ethanol abusers is associated with neutropenia. We hypothesize that ethanol accelerates the apoptosis of neutrophils thus decreasing the peripheral blood count of neutrophils. We studied the effect of ethanol on neutrophil apoptosis in vivo as well as in vitro. Human neutrophils harvested from healthy subjects after an alcohol drinking binge showed enhanced apoptosis (before, 0.5 ± 0.25 vs. after, 26.1 ± 2.6% apoptotic neutrophils/field). Peritoneal neutrophils isolated from ethanol‐treated rats also showed increased ( P < 0.0001) apoptosis when compared with neutrophils isolated from control rats (control, 0.8 ± 0.2% vs. ethanol, 11.8 ± 0.7% apoptotic neutrophils/field). In in vitro studies, ethanol in concentrations of 50 mM and higher accelerated the apoptosis of human and rat neutrophils. This effect of ethanol on human neutrophils was time dependent. DNA isolated from ethanol‐treated human neutrophils displayed integer multiples of 180 base pairs (ladder pattern), further confirming the effect of ethanol on neutrophil apoptosis. N G ‐monomethyl‐l‐arginine monoac‐etate and N G ‐nitro‐L‐arginine methyl ester, inhibitors of nitric oxide (NO) synthase, attenuated the ethanol‐induced neutrophil apoptosis. Sodium nitroprusside, a NO donor, also promoted neutrophil apoptosis. Moreover, ethanol enhanced neutrophil expression of inducible NO synthase. In addition, ethanol stimulated neutrophil NO generation. These results suggest that ethanol accelerates neutrophil apoptosis. This effect of ethanol on neutrophil apoptosis seems to be mediated through the generation of NO. J. Leukoc. Biol. 66: 930–936; 1999.