Calcium Signaling in Pancreatic Immune CellsIn situ

AbstractImmune cells were identified in intact live mouse pancreatic lobules and their Ca2+ signals, evoked by various agents, characterized and compared with the simultaneously recorded Ca2+ signals in neighboring acinar and stellate cells. Immunochemistry in the live lobules indicated that the pancreatic immune cells most likely are macrophages. In the normal pancreas the density of these cells is very low, but induction of acute pancreatitis (AP), by a combination of ethanol and fatty acids, markedly increased the number of the immune cells. The principal agent eliciting Ca2+ signals in the pancreatic immune cells was ATP, but these cells also frequently produced Ca2+ signals in response to acetylcholine and to high concentrations of bradykinin. Pharmacological studies, using specific purinergic agonists and antagonists, indicated that the ATP-elicited Ca2+ signals were mediated by both P2Y1 and P2Y13 receptors. The pancreatic immune cells were not electrically excitable and the Ca2+ signals generated by ATP were primarily due to release of Ca2+ from internal stores followed by store-operated Ca2+ entry through Ca2+ release-activated Ca2+ channels. The ATP-induced intracellular Ca2+ liberation was dependent on both IP3 generation and IP3 receptors. We propose that the ATP-elicited Ca2+ signal generation in the pancreatic immune cells is likely to play an important role in the severe inflammatory response to the primary injury of the acinar cells that occurs in AP.