The Role of Gap Junctional Communication in Cerulein-Induced Acute Pancreatitis

Gap junction channels contribute to the maintenance of tissue homeostasis by allowing a regulated pathway for the direct exchange of ions and second messengers between neigh- bouring cells. These channels are comprised of Connexin (Cx) subunits. In the pancreas, acinar cells are extensively coupled through Cx32 and Cx26 channels. Cx32 deficiency is associated with enhanced basal amylase secretion both in vitro and in vivo. To explore the possible role of Cx32 channels in acinar cell response to injury, we studied the severity of cerulein-induced acute pancreatitis in mice which were deficient in Cx32. Methods: Cx32 deficient mice were generated by gene targeted deletion of gene encod- ing Connexin 32. These mice were then compared to wild type controls. Acute pancre- atitis was induced by giving mice 10 hourly injections of cerulein (50g/Kg). The severity of pancreatitis was assessed by measuring serum amylase activity, pancreatic water content, pancreatic neutrophil sequestration, (i.e. myeloperoxidase activity) and by morphometric estimation of the extent of acinar cell necrosis. Results: The severity of pancreatitis, as judged by each of these parameters, was dra- matically increased in Cx32 deficient mice. Furthermore, two mice died during the experiment with massive pancreatic necrosis. Conclusions: These results indicate that severity of the disease is linked to the integrity of acinar cell gap junction channels. This novel role for gap junction channels may have important implications not only for the understanding of acute pancreatitis, but possi- bly also of other acute and chronic inflammatory diseases like hepatitis, atherosclerosis and cystic fibrosis. Pancreatology 2002;2:217-361