Alcoholic liver injury in baboons: transformation of lipocytes to transitional cells

Abstract

Ultrastructure of the lipocytes (the main perisinusoidal cells) and their alterations in the progression of hepatic fibrosis were studied in liver biopsy specimens of baboons pair-fed with diets containing alcohol, or isocaloric carbohydrate, for up to 112 mo. In control baboons, 97% of the cells in the Disse space were lipocytes characterized by a volume density of lipid droplets occupying greater than 20% of the cell volume and by the presence of microfilament bundles with associated dense bodies and pinocytic vesicles. Intercellular junctions of the adherens type were present between lipocytes and hepatocytes. After alcohol consumption, the number of lipocytes (as assessed by light microscopy) was significantly decreased in fatty livers and at various stages of hepatic fibrosis; this was associated with a decreased hepatic vitamin A content. In baboons fed alcohol, only 48% of cells were lipocytes, whereas 52% were transitional cells defined by a volume of lipid droplets less than 20% of the cell. Like the lipocytes, transitional cells exhibited microfilament bundles, dense bodies, and pinocytic vesicles, and were attached to the hepatocytes by cell junctions. The rough endoplasmic reticulum in transitional cells was conspicuous and had an area significantly greater than that in lipocytes of controls and alcohol-fed animals (69% and 37%, respectively). There was a significant correlation between the percentage of transitional cells as well as the area of their rough endoplasmic reticulum and the degree of hepatic fibrosis. Thus, in baboons fed alcohol, the progression of hepatic fibrosis is associated with transformation of lipocytes to transitional cells characterized by a depletion of lipid droplets and a hypertrophy of the rough endoplasmic reticulum; these transitional cells may play a role in promoting hepatic fibrosis in alcoholic liver injury.