Calcium Signaling in Pancreatic Immune Cells In situ

Immune 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.