Chronic Ethanol Consumption Enhances Endotoxin Induced Hepatic Sinusoidal Leukocyte Adhesion

In alcoholic liver disease, endotoxin has been postulated to play an important role in its pathogenesis. Endotoxin is known to lead to impediment of hepatic microcirculation, including the adhesion of leukocytes to sinusoidal endothelial cells. In this study, the effect of chronic ethanol consumption on the leukocyte adhesion elicited by endotoxin was examined. Male Wistar rats were pair-fed with a liquid diet containing ethanol or an isocaloric control diet for 6 weeks. The liver of anesthetized rats were placed on the nonfluorescent cover-glass for observation by an intravital inverted microscope equipped with a silicon intensified target camera. The red blood cell (RBC) velocity in hepatic sinusoids was measured by an off-line temporal correlation velocimeter (Capiflow, Sweden) after intravenous injection of fluorescein isothiocyanate-labeled rat RBC. RBC velocity in sinusoids was more severely disturbed in ethanol fed rats than in controls. Leukocytes were stained by the intravenous injection of carboxyfluorescein succinimidyl ester for a fluorographic observation of leukocyte adhesion. After lipopolysaccharide injection, the number of adherent leukocytes was significantly greater in ethanol-fed rats than in controls. Plasma tumor necrosis factor-alpha levels were also higher in ethanol-fed rats than in controls. These results suggest that chronic ethanol consumption aggravates endotoxin induced leukocytes adhesion that may result in hepatic microcirculatory disturbances. Leukocyte adhesion to the sinusoidal wall may be associated with increased in tumor necrosis factor-alpha levels.