Apoptosis of mouse pancreatic acinar cells after duct ligation

Abstract

It has been established that pancreatic exocrine acinar cells disappear after pancreatic duct obstruction. This study aimed to examine the relationship between the disappearance of the acinar cells and apoptosis after pancreatic duct ligation of the splenic lobe in dd-mice, six weeks of age. In some mice, the ligature was removed after two or three days. In addition to general light and electron microscopic examinations on the pancreatic tissues, paraffin sections stained with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method were observed to detect nuclear DNA fragmentation. Pancreatic acinar cells underwent apoptosis initiated with nuclear DNA damages three days after duct ligation and were completely deleted by seven days. Due to the elevation of the intraluminal pressure, the acinar cells showed interrupted secretion of their zymogen granules and disorganization of their rough endoplasmic reticulum, causing the cessation of granule formation before apoptosis started. These cytoplasmic changes prior to apoptosis are reversible, as observed after removal of the ligation. Apoptosis of the acinar cells was indentified by TUNEL-labeling of the nuclei, the condensation and margination of nuclear chromatin, and round fragmentation of cell bodies, all irreversible changes. Apoptosis of acinar cells seemed to stimulate the proliferation of duct cells, which comprised the main cell components in the exocrine pancreas after the disappearance of acinar cells.