ACUTE ALCOHOL ADMINISTRATION TO MICE INDUCES HEPATIC SINUSOIDAL ENDOTHELIAL-CELL DYSFUNCTION

Ethanol administration to mice (4.4 g kg(-1) body wt., i.p.) induced a marked increase (125%) in plasma hyaluronan (HA) concentration associ ated with a significant decrease (46%) in HA uptake by the isolated, p erfused liver. Similar changes were obtained after i.v. administration of Escherichia coli lipopolysaccaharide (1 mg kg(-1) body wt.), a str ong activator of Kupffer cells. Since: (a) hepatic HA uptake is predom inantly a function of the sinusoidal endothelial cells, reflecting the ir functional stale, and (b) liver is a major site of HA clearance fro m the blood, we conclude that alcohol alters sinusoidal endothelial ce ll functions, including HA endocytosis. Changes in Kupffer cell functi onal state may be a primary event underlying the effects of both ethan ol and LPS on sinusoidal endothelial cells.