EFFECT OF OBSTRUCTIVE CHOLESTASIS ON MEMBRANE TRAFFIC AND DOMAIN-SPECIFIC EXPRESSION OF PLASMA-MEMBRANE PROTEINS IN RAT-LIVER PARENCHYMAL-CELLS

We investigated the effect of bile duct ligation and its release on me mbrane traffic and plasma membrane protein distribution in rat hepatoc ytes. Immunofluorescence studies with monoclonal antibodies against si x domain-specific surface antigens revealed that bile duct ligation le ads to an accumulation of pericanalicular vesicles containing canalicu lar antigens. All apical antigens could be demonstrated in the basolat eral plasma membrane, whereas only one out of three basolateral antige ns redistributed to the canalicular plasma membrane. After release of bile duct ligation, the accumulated pericanalicular vesicles disappear ed within minutes, whereas the plasma membrane polarity was not restor ed within 1 hr. Monitoring secretion of polymeric IgA and horseradish peroxidase into bile demonstrated that bile duct ligation also inhibit s the transcytotic vesicle pathway and severely impairs the function o f tight junctions. In contrast, bile duct ligation appears not to affe ct the endoplasmic reticulum to basolateral membrane traffic as assess ed by determination of newly synthesized albumin and transferrin in se rum nor does it influence receptor mediated endocytosis at the basolat eral plasma membrane.