Defined Localization of Nestin-expressing Cells in l-arginine-induced Acute Pancreatitis

Abstract

Nestin is a stem cell marker originally described as an intermediate filament protein expressed in neuroepithelial stem cells. In the pancreas, a small number of nestin-expressing cells, which are believed to represent either stem cells or progenitor cells, are known to be present in islets, as well as in some stellate cells, pericytes, and endothelial cells. We monitored pancreatic nestin expression to delineate the location of stem cells/progenitor cells in the pancreas after L-arginine-induced pancreatitis. Male Wistar rats received 2 intraperitoneal injections of L-arginine, each consisting of 250 mg/100 g of body weight, and were killed 3, 6, and 12 hours and 1, 4, 7, and 14 days later. Serum amylase and lipase levels increased after L-arginine injection, maximal levels occurring at 3 and 12 hours postinjection, respectively. Six hours after L-arginine injection, interstitial edema was observed in the pancreas, whereas on day 4 postinjection, there was severe pancreatic necrosis. Neovascularization and ductal-ductular proliferation were also present in the pancreas. Immunohistochemical analysis revealed increased Ki-67 labeling in acinar cells and capillary endothelial cells. Immunoblotting using antinestin antibody revealed increased nestin expression after L-arginine injection. In the control rat pancreas, nestin immunoreactivity was detected in a few capillary endothelial cells in some islets. After L-arginine injection, nestin was expressed in proliferating capillary endothelial cells, in stellate cells surrounding ductular structures and in submesothelial cells. Transient nestin expression occurs in specific cell types during the proliferative stage after recovery from L-arginine-induced pancreatitis and may represent the contribution of stem cells and/or progenitor cells to the regenerative capacity of the pancreas.