CHARACTERIZATION OF A CHICKEN HEPATOMA-CELL LINE WITH A SPECIFIC DEFECT IN FIBRINOGEN SECRETION

This study characterizes plasma protein synthesis and its hormonal reg ulation in a chicken hepatoma cell line, with particular emphasis on f ibrinogen. Whereas virtually all aspects of hemopexin, transferrin and albumin production in these cells corresponded to those of cultured p rimary hepatocytes, fibrinogen was not secreted. Analysis of fibrinoge n subunit synthesis revealed a specific defect in synthesis of one sub unit, gamma, correlating with a lack of its mRNA. Pulse-chase and elec tron microscopic studies demonstrate that, despite the inability of th ese cells to secrete the A alpha and B beta subunits produced, there i s no long-term accumulation of unsecreted fibrinogen. The B beta fibri nogen subunits are largely degraded 2 hr after synthesis. During this time, approximately half of the A alpha subunits are degraded; the res t are converted to the glycosylated form. The implications of this typ e of defect with respect to the pathogenesis of fibrinogen storage dis ease are discussed.