Plasma kininogen deficiency: associated defective secretion of kininogens by primary cultures of hepatocytes from brown Norway Katholiek rats.
To clarify the mechanism of plasma kininogen deficiency of Brown Norway Katholiek strain (B/N-Katholiek) rats, we compared synthesis and secretion of kininogens by primary cultures of hepatocytes from B/N-Katholiek and B/N-Kitasato (normal strain) rats. Pulse-and-chase experiments using [35S]methionine demonstrated that kininogen antigens with molecular masses of 100 and 66 kDa, corresponding to high- and low-molecular-weight kininogens (HK and LK), respectively, were detected in the hepatocytes of both strains. These proteins were then processed to 108- and 71-kDa forms, respectively, and secreted by the normal hepatocytes, while the latter forms were hardly secreted in the culture media of the deficient hepatocytes. However in the deficient cells, 100- and 66-kDa forms were accumulated, but 108- and 71-kDa bands were faint. A subcellular fractionation study showed that a relatively higher amount of the kininogen antigens was present in the lysosomal fraction of B/N-Katholiek hepatocytes than in that of B/N-Kitasato hepatocytes. From these results we postulate the cause of the secretion defect of B/N-Katholiek liver to be as follows. (i) B/N-Katholiek liver could synthesize the mature secretable forms of HK and LK, but they are too rapidly transported to the lysosomes, or (ii) the mature forms in B/N-Katholiek hepatocytes might be synthesized much more slowly than those in the normal cells. T-Kininogen was normally synthesized and secreted by the hepatocytes of B/N-Katholiek, suggesting that the secretion defect could be limited to HK and LK, at a common site.