ACUTE ETHANOL INTOXICATION INHIBITS NEUTROPHIL BETA(2)-INTEGRIN EXPRESSION IN RATS DURING ENDOTOXEMIA

The effects of acute ethanol intoxication on neutrophil [polymorphonuc lear leukocyte (PMN)] adhesion molecule expression and certain other f unctional properties during endotoxemia were studied in rats to elucid ate the mechanisms underlying the immunosuppressive effects of ethanoi . Acute ethanol intoxication was induced by an intraperitoneal injecti on of 20% ethanol at a dose of 5.5 g of ethanol/kg. Control animals re ceived an intraperitoneal injection of saline. Thirty minutes after in traperitoneal injection, animals were given a 90-min intravenous infus ion of Escherichia coli endotoxin (total dose of 112.5 mu g/rat in 25 mi of saline) or saline. Certain rats received granulocyte colony-stim ulating factor (G-CSF; 50 mu/kg in 5% dextrose, subcutaneous injection twice daily) or vehicle pretreatment for 2 days before intravenous en dotoxin infusion. Endotoxemia significantly upregulated CD11b/c and CD 18 expression on PMNs when compared with those of saline-infused rats. Acute ethanol intoxication inhibited this endotoxin-induced upregulat ion of CD11b/c and CD18 expression on PMNs. Ethanol intoxication also suppressed the phagocytic activities of PMNs in saline-infused rats, b ut this suppression failed to reach statistical significance in endoto xin-infused rats. Hydrogen peroxide generation by PMNs in saline-or en dotoxin-infused rats was not affected by ethanol intoxication. Histolo gical examination showed extensive PMN sequestration in the liver afte r endotoxin infusion, and ethanol intoxication significantly attenuate d this hepatic sequestration of PMNs. G-CSF pretreatment enhanced neut rophil phagocytosis, CD11b/c and CD18 expression in endotoxin-infused rats, and prevented the ethanol-induced inhibition of neutrophil Cola expression and phagocytosis. The impairment of beta(2)-integrin expres sion on PMNs may be one mechanism underlying ethanol-induced defects o f neutrophil delivery into tissue sites of infection. G-CSF may be of benefit to the infected alcoholic host by enhancing leukocyte defense functions.