CHRONIC ALCOHOL-INTOXICATION ENHANCES THE EXPRESSION OF CD18 ADHESIONMOLECULES ON RAT NEUTROPHILS AND RELEASE OF A CHEMOTACTIC FACTOR BY KUPFFER CELLS

Chronic alcohol intoxication has been associated with increased migrat ion of inflammatory leukocytes to the liver that may contribute to the development of alcoholic hepatitis in susceptible individuals. Thus, this work was performed to examine the mechanism by which neutrophils [polymorphonuclear neutrophils (PMNs)] are sequestered in the liver du ring prolonged consumption of alcohol. Male Sprague-Dawley rats were f ed with Sustacal supplemented by 36% alcohol, or isocaloric diet for 1 6 weeks. Circulating blood PMNs were collected and examined for CD18 ( beta(2)-integrin) adhesion molecule expression, Monoclonal antibody 1F 12, an anti-CD18 antibody and potent neutropenic agent, was used to de tect CD18 on PMNs, More than 97% of neutrophils obtained from pair and ethanol-fed rats were positive for the antibody, Fluorescence intensi ty of fluorescein isothiocyanate-1F12 binding to PMNs from ethanol-fed rat was significantly enhanced 2-fold compared with the pair-fed cont rols. The release of chemoattractant and free radical-generating activ ity in culture supernatants of Kupffer cells was also examined. Twenty -four hr culture supernatants of Kupffer cells from chronic alcoholic rats enhanced the migration and superoxide anion generation by normal PMNs, compared with those of the pair-fed rats, Antirat interleukin-8 antiserum inhibited chemotactic activity and superoxide generating cap acity of culture supernatants. These results suggest that upregulation of adhesion molecules on PMNs and chemotactic factor release from Kup ffer cells may contribute, at least in part, to enhanced migration of inflammatory leukocytes to the liver during chronic alcohol intoxicati on.