THE PANCREATIC DUCT EPITHELIUM IN-VITRO - BILE-ACID INJURY AND THE EFFECT OF EPIDERMAL GROWTH-FACTOR

Background. Pancreatic duct epithelial cells form a barrier against pa renchymal injury. The capacity of these cells to respond to injury has not been investigated. We hypothesized that epidermal growth factor ( EGF), normally found in pancreatic juice, could protect the duct epith elium from damage. Methods. An explant system of duct cell culture dev eloped in our lab with the bovine main pancreatic duct was used. Expla nts were exposed to bile acid (taurodeoxycholic acid [TDCA] 0, 0.05, 0 .5, and 1 mmol/L) in the presence or absence of EGF (0, 1, 10, and 100 nmol/l) for 48 hours. Epithelial proliferation, damage, and growth ou t from the explant edge were assessed histologically. Expression of du ctal markers and the extent of cell proliferation were determined by i mmunohistochemistry using specific antibodies. Results. Explant duct c ells proliferated and demonstrated continued expression of key duct an tigens in culture. TDCA produced dose-dependent mucosal damage and red uced epithelial density and growth from the edge. EGF increased cellul ar density in the native epithelium, but did not significantly alter g rowth from the edge. Mucosal damage created by TDCA exposure was signi ficantly decreased with EGF and both growth from the edge and cell den sity were preserved. Conclusions. Explants created om the bovine main pancreatic duct serve as an excellent model for the study of duct epit helial cells in vitro. These cells proliferate in response to EGF and are damaged by TDCA at concentrations below those normally associated with detergent-like activity and below levels observed in bile anti du odenal secretions. The ability of EGF to protect from this injury sugg ests a potential physiologic role in the maintenance of the pancreatic duct mucosal barrier.