We have used crossed immunoelectrophoresis to identify and establish the relative amounts of serum proteins secreted by a differentiated cell line (Fao) derived from a Reuber H35 rat hepatoma. Our results show that these cells secrete at least 15 plasma proteins. Ten of these: albumin, alantitrypsin, al-lipoprotein, al-macroglobulin, al-antichymotrypsin, GC-globulin (transcalciferin), fibronectin, hemopexin, transferrin and the Cs component of complement have been identified. To examine the feasibility of using the Fao cell line as a model for studies on the regulation of hepatic protein secretion, we measured the relative amounts of 10 serum proteins secreted into the growth medium after exposure of these cells to dibutyryl cyclic AMP, hydrocortisone and a combination of both compounds. We also examined the effects of growth temperature (33.5', 37' and 39'C) and the removal of fetal calf serum from the growth medium on the relative amounts of these proteins secreted. We found that the rates of secretion of most of the serum proteins were altered by one or more of the treatments used in these experiments. In addition, detectable levels of secretion of three serum proteins, fibronectin and two unidentified, occurred only under certain of the experimental conditions. These results demonstrate that the pattern of proteins secreted from Fao cells can be experimentally altered and indicate that this cell line may be a useful model for studies on the control of hepatic protein secretion.
Significant changes in the relative amounts of plasma proteins synthesized and secreted by the liver are among the physiological responses to tissue trauma (1). These changes are variable depending upon the type and magnitude of insult to the tissue (2). Following injury, the levels of some plasma proteins, the acute phase proteins, rise dramatically, the levels of other proteins remain constant, and still others decrease (1). A number of effectors, including mediators synthesized by blood cells at the site of tissue damage (3), steroid (4,5) and peptide (6, 7) hormones, CAMP ( 5 ) and peptides produced by proteolysis of certain of the plasma proteins (8), have been reported to influence the rate of hepatic synthesis and secretion of plasma proteins. The preceding observations suggest that the levels of individual or perhaps classes of plasma proteins are regulated by mechanisms utilizing one or more effectors. The composite of plasma proteins, however, appears to be determined by the combined action of a variety of effectors. Due to the complexities of the mechanisms regulating plasma protein