Uncoupling of the secretory pathways for IgA and secretory component by cholestasis

Circulating polymeric immunoglobulin A (IgA) binds to secretory component (SC) on the surface of rat hepatocytes and is internalized and transported by vesicles to the canalicular membrane where the IgA-SC complex is secreted into bile. To further characterize this transport pathway, we examined the effects of bile flow reduction or transient bile duct obstruction on the secretion of IgA and SC into bile. In response to gradually increasing resistance to bile flow, the biliary concentration of IgA decreased as bile flow decreased, whereas total biliary protein concentration was little changed. After 2 h of bile duct clamping, the amount of IgA secreted into bile during the postclamp period was decreased to one-tenth of control values. Similarly, transport of biosynthetically labeled monoclonal IgA ([3H]MoIgA) during the postclamp period was reduced three-fold. In contrast to the impairment in IgA secretion, secretion of SC continued at nearly normal levels after resumption of bile flow. The reduced transport of IgA was not due to a failure of IgA to reach the hepatocyte, a functional alteration of the IgA, or a decrease in the number of hepatic IgA receptors. Our studies indicate that secretion of IgA is sensitive to bile flow and that the biliary secretory pathways for IgA and SC are dissociated after brief periods of cholestasis.