CD14 AND LIPOPOLYSACCHARIDE-BINDING PROTEIN EXPRESSION IN A RAT MODELOF ALCOHOLIC LIVER-DISEASE

Lipopolysaccharide-binding protein (LBP) and CD14 play key intermediar y roles in the activation of cells by endotoxin. As endotoxin has been postulated to participate in promoting pathological liver injury in a lcoholic liver disease, we investigated the role of LBP and CD14 in al coholic liver injury. Rats were fed intragastrically ethanol or dextro se and either medium-chain triglycerides, corn oil, or fish oil for 4 weeks. Kupffer cells, endothelial cells, and hepatocytes mere isolated . LBP and CD14 mRNA levels were measured in liver and individual cell types. The highest levels of LBP and CD14 mRNA levels In the Liver wer e found in the fish oil/ethanol group, which was also the group with t he greatest degree of pathological injury and inflammation. CD14 mRNA levels were also significantly elevated in groups fed unsaturated fatt y acids with dextrose. CD14 expression was localized to the Kupffer ce lls and LBP expression to the hepatocytes. Expression of CD14 mRNA was also found in nonmyeloid cells in the two experimental groups (fish o il/ethanol and corn oil/ethanol) that had liver necrosis and inflammat ion. Our results suggest that enhanced LBP and CD14 expression correla tes with the presence of pathological liver injury in alcoholic liver injury. Furthermore, unsaturated fatty acids may prime cells to respon d to endotoxin by enhancing CD14 expression.