ETHANOL-INDUCED LEUKOCYTE ADHERENCE AND ALBUMIN LEAKAGE IN RAT MESENTERIC VENULES - ROLE OF CD18 INTERCELLULAR ADHESION MOLECULE-1/

The adherence and emigration of leukocytes have been implicated as a r ate-limiting step in the microvascular disturbance in a variety of pat hogenic events. The objective of the present study was to investigate leukocyte-endothelial cell adhesion and endothelial barrier function i n rat mesenteric microvessels exposed to ethanol, which is known to ca use inflammation and injury in various organs. Mesentery of male Wista r rats was used for intravital microscopic observations. Leukocyte adh erence and albumin leakage were monitored in single postcapillary venu les using the intravital fluorescence microscope. Superfusion of 50 mM ethanol elicited the leukocyte adherence and albumin leakage within 6 0 min. Pretreatment with a monoclonal antibody directed against either CD18 or intercellular adhesion molecule-1 (ICAM-1) significantly prev ented the ethanol-induced increase in leukocyte adherence and decrease in barrier function of endothelium. These results suggest that ethano l-induced leukocyte adherence is mediated by CD18 on leukocytes and IC AM-1 on endothelial cells. The present study further supports that CD1 8/ICAM-1-dependent leukocyte-endothelial adhesive interactions lead to macromolecular leakage in the postcapillary venules exposed to ethano l.