Intracellular Calcium Affects Neutrophil Chemoattractant Expression by Macrophages in Rats with Cerulein-Induced Pancreatitis

Abstract Pancreatitis complicated with infection oftenresults in the development of multiple organ failure. Weinvestigated the role of altered intracellular calciumas a priming signal for cytokine-induced neutrophil chemoattractant expression in this process.Agents modulating cytosolic Ca2+ wereutil...
Ausführliche Beschreibung

Abstract Pancreatitis complicated with infection oftenresults in the development of multiple organ failure. Weinvestigated the role of altered intracellular calciumas a priming signal for cytokine-induced neutrophil chemoattractant expression in this process.Agents modulating cytosolic Ca2+ wereutilized to study the in vivo and in vitrocytokine-induced neutrophil chemoattractant expressionfor macrophages in rats with cerulein-induced pancreatitis afterintraperitoneal administration of lipopolysaccharide asa septic challenge. Pretreatment with the calciumchannel blocker verapamil significantly reduced serumcytokine-induced neutrophil chemoattractant concentrations inrats with cerulein-induced pancreatitis after septicchallenge. Lipopolysaccharide-stimulated in vitrocytokine-induced neutrophil chemoattractant (CINC)production by peritoneal macrophages was significantlyenhanced by pretreatment with thapsigargin (an inhibitorof the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (acalcium-specific ionophore, extracellular Ca2+ influx). Pretreatment withU73122 (a phospholipase C inhibitor) inhibitedlipopolysaccharide-stimulated but not basalcytokine-induced neutrophil chemoattractant production,while verapamil (a calcium channel blocker), TMB-8 (an inhibitor ofcalcium release from endoplasmic reticulum), and W7(calmodulin antagonist) completely abrogated thechemoattractant production. Altered intracellularcalcium, due to Ca2+ efflux from intracellularstores, may be involved in the “priming” ofmacrophages to release cytokine-induced neutrophilchemoattractant following triggering withlipopolysaccharide during acute cerulein pancreatitis. Ausführliche Beschreibung