Deletion of hyperplastic biliary epithelial cells by apoptosis following removal of the proliferative stimulus

Regression of bile ductular hyperplasia following elimination of the proliferative stimulus is widely recognised but the mode of deletion of the excess biliary epithelial cells (BEC) is not understood. Apoptosis, a process of cell death distinct from coagulative necrosis, is known to be involved in both atrophy and physiological involution of various organs. Therefore, a time course histological study was made of the frequency of apoptosis among BEC following removal of the proliferative stimulus in two rat models of BEC hyperplasia produced by the feeding of alpha-naphthyl isothiocyanate (ANIT) for 6 weeks or the ligation of the common bile duct for 5 weeks. In the former, the rats were returned to a normal diet after 6 weeks and in the latter, the total biliary obstruction (TBO) was relieved by a Roux-en-Y choledochojejunostomy. As it has been reported that apoptotic bodies in glandular tissues may be extruded into acinar lumina to be lysed or washed away, thereby reducing chances of their detection in histological preparations, in a third experiment bile was collected for 22 h following relief of TBO of 7 days' duration. The centrifuged pellet of bile was studied by electron microscopy. In both models, throughout the 21 days of observation following removal of the stimulus, apoptotic bodies were found between or as phagocytosed bodies within BEC. The frequency of apoptotic bodies peaked at 3 days corresponding with a rapid reduction in the number of BEC during the first 3 days followed by a much slower rate of deletion in the succeeding 18 days of observation. Electron microscopy of the centrifuged pellet of bile revealed apoptotic bodies. It is concluded that deletion of excess BEC during regression of BEC hyperplasia occurs principally by apoptosis.