CHRONIC ETHANOL-CONSUMPTION ENHANCES ENDOTOXIN-INDUCED HEPATIC SINUSOIDAL LEUKOCYTE ADHESION

In alcoholic liver disease, endotoxin has been postulated to play an i mportant role in its pathogenesis. Endotoxin is known to lead to imped iment of hepatic microcirculation, including the adhesion of leukocyte s to sinusoidal endothelial cells. In this study, the effect of chroni c ethanol consumption on the leukocyte adhesion elicited by endotoxin was examined. Male Wistar rats were pair-fed with a liquid diet contai ning ethanol or an isocaloric control diet for 6 weeks. The liver of a nesthetized rats were placed on the nonfluorescent cover-glass for obs ervation by an intravital inverted microscope equipped with a silicon intensified target camera. The red blood cell (RBC) velocity in hepati c sinusoids was measured by an off-line temporal correlation velocimet er (Capiflow, Sweden) after intravenous injection of fluorescein isoth iocyanate-labeled rat RBC. RBC velocity in sinusoids was more severely disturbed in ethanol fed rats than in controls. Leukocytes were stain ed by the intravenous injection of carboxyfluorescein succinimidyl est er for a fluorographic observation of leukocyte adhesion. After lipopo lysaccharide injection, the number of adherent leukocytes was signific antly greater in ethanol-fed rats than in controls. Plasma tumor necro sis factor-alpha levels were also higher in ethanol-fed rats than in c ontrols. These results suggest that chronic ethanol consumption aggrav ates endotoxin induced leukocytes adhesion that may result in hepatic microcirculatory disturbances. Leukocyte adhesion to the sinusoidal wa ll may be associated with increased in tumor necrosis factor-alpha lev els.