Selective intracellular degradation of fibrinogen and its reversal in cultured hepatocytes.

Abstract

Primary monolayer cultures of chick embryo hepatocytes were employed in pulse-chase experiments to examine plasma protein synthesis and secretion. The fates of [35S]methionine-labeled fibrinogen and transferrin were monitored in cell extracts and in spent culture media. It was found that hepatocytes, which were maintained in the absence of added hormones or serum, released into the medium virtually all of the label of transferrin but only 30% of the label in fibrinogen. The remainder of the labeled fibrinogen was retained by the cells, gradually disappearing in a manner suggestive of its intracellular degradation. To stimulate fibrinogen production on as many levels as possible, fetal bovine serum was added to the medium of the cultured cells. Serum elicited an increase in the level of fibrinogen mRNA which was accompanied by a 7-fold increase in the rate of fibrinogen synthesis as well as the complete release of fibrinogen label, resulting in an overall 20-fold enhancement in the hepatocellular output of this protein. Thus, both the amount of fibrinogen synthesized as well as the amount ultimately secreted are subject to modulation by the hepatocellular environment.