Regulation of hyaluronate synthesis in rat liver fat storing cell cultures by Kupffer cells.

During fibrogenesis in chronically inflamed liver the concentration of extracellular matrix hyaluronate increases several-fold, but the mechanism of hyaluronate accumulation has hitherto been unknown. We studied the effect of stimulated Kupffer cells on the synthesis and secretion of hyaluronic acid by rat liver fat storing cells, the main hyaluronate-producing cell type in liver. Conditioned medium was harvested from monolayers of Kupffer cells activated by exposure for 24 h to zymosan and lipopolysaccharide. Addition of these Kupffer cell media to monolayers of fat storing cells stimulated more than 2-fold the incorporation of [3H]glucosamine into both total glycosaminoglycans and hyaluronic acid in the medium. The synthesis rate of hyaluronic acid was enhanced more strongly than that of sulfated glycosaminoglycans, resulting in a significant fractional increase of hyaluronate. The concentration of hyaluronate measured with a radiometric assay in the medium of fat storing cells exposed to Kupffer cell media was raised 2.6-fold within 24 h in comparison to untreated cultures. The synthesis rate of hyaluronate in untreated fat storing cells of 4.2 +/- 0.8 micrograms/mg DNA per h increased up to 8.2 +/- 0.9 micrograms/mg DNA per h in the presence of Kupffer cell conditioned medium. The results demonstrate an activation of hyaluronate synthesis in fat storing cells by Kupffer cell factor(s), a mechanism which might be of relevance for the strong absolute and fractional increase of hyaluronate in the extracellular matrix of fibrotic livers.