Chemotactic LTB4 metabolites produced by hepatocytes in the presence of ethanol

Ethanol in low concentrations significantly alters the hepatocyte metabolism of the neutrophil chemotactic lipid leukotriene B4 (LTB4). Two novel metabolites of LTB4 which are encountered only when ethanol is present, retained significant biological activity. One metabolite, 3-hydroxy-LTB4 increased intracellular free calcium in the human neutrophil at concentrations as low as 3 x 10(-10) M as well as induced shape change and adherence to albumin-coated latex beads at 10 nM. The 3-hydroxy-LTB4 and 3,20-hydroxy-LTB4 metabolites were also potent chemotactic agonists with an ED50 at 3.0 and 9.0 nM, respectively. These results suggest that the presence of ethanol can substantially alter inactivation of LTB4 by the liver and may mediate neutrophil accumulation into the liver, thereby contributing to the pathogenesis of alcoholic hepatitis even when LTB4 biosynthesis occurs at some site distant to the liver.