Chronic alcohol intoxication enhances the expression of CD18 adhesion molecules on rat neutrophils and release of a chemotactic factor by Kupffer cells.
Chronic alcohol intoxication has been associated with increased migration 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 during prolonged consumption of alcohol. Male Sprague-Dawley rats were fed with Sustacal supplemented by 36% alcohol, or isocaloric diet for 16 weeks. Circulating blood PMNs were collected and examined for CD18 (beta 2-integrin) adhesion molecule expression. Monoclonal antibody 1F12, an anti-CD18 antibody and potent neutropenic agent, was used to detect CD18 on PMNs. More than 97% of neutrophils obtained from pair and ethanol-fed rats were positive for the antibody. Fluorescence intensity of fluorescein isothiocyanate-1F12 binding to PMNs from ethanol-fed rat was significantly enhanced 2-fold compared with the pair-fed controls. The release of chemoattractant and free radical-generating activity 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 capacity of culture supernatants. These results suggest that upregulation of adhesion molecules on PMNs and chemotactic factor release from Kupffer cells may contribute, at least in part, to enhanced migration of inflammatory leukocytes to the liver during chronic alcohol intoxication.
Bautista
A P
AP
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112, USA.
D000435:Alcoholic Intoxication / Q000276:immunology*; D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006519:Hepatitis, Alcoholic / Q000276:immunology*; D016209:Interleukin-8 / Q000502:physiology; D007728:Kupffer Cells / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D018821:CD18 Antigens; D002630:Chemotactic Factors; D016209:Interleukin-8; D013481:Superoxides