Gender differences in phagocytic responses in the blood and liver, and the generation of cytokine-induced neutrophil chemoattractant in the liver of acutely ethanol-intoxicated rats

Phagocytosis by circulating and liver-recruited polymorphonuclear leukocytes (PMNs) and Kupffer cells was studied in acutely ethanol intoxicated, age-matched male and female rats. Acute ethanol intoxication in female rats is associated with a more effective phagocytic PMN response in the circulating blood, but with lower phagocytic activities by liver-recruited PMNs and Kupffer cells than in their male counterparts. Endotoxin [lipopolysaccharide (LPS)] treatment (consisting of a 90-min intravenous infusion of a nonlethal dose) of acutely ethanol-intoxicated male and female rats results in enhanced phagocytic responses in liver-sequestered PMNs and Kupffer cells, but not in circulating PMNs. However, the LPS challenge elicits a lesser phagocytic response in liver PMNs and Kupffer cells of female rats than in males. Significant gender differences exist in the extent of hepatic PMN infiltration in ethanol plus LPS-treated rats, which is paralleled by very similar differences in CD11b/c adhesion molecule expression in circulating PMNs and cytokine-induced neutrophil chemoattractant generation by hepatocytes and Kupffer cells. Taken together, these data indicate a smaller phagocytic response to fight infection in the liver of acutely alcohol-intoxicated female rats, but also a mechanism to afford some protection against neutrophil-associated tissue injury.