Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis

Bile Acids Induce Pancreatic Acinar Cell Injury and Pancreatitis by Activating Calcineurin

“…The two phenomena appear to be independent and mediated by different factors (62)(63)(64). Awla et al (61) use the pharmacologic inhibitor CsA to demonstrate the importance of calcineurin pathways.…”

Calcium signalling and pancreatic cell death: apoptosis or necrosis?

“…The latter triggers acute exudative inflammation of the surrounding tissue; subsequent activation and infiltration of neutrophils is thought to increase intracellular digestive enzyme activation and exacerbate pancreatitis. 22 Over a decade ago we proposed that abnormal, prolonged elevation of cytosolic Ca 2 þ is the crucial trigger of pancreatitis. 23 Under physiological conditions, Ca 2 þ is tightly regulated in discrete cellular microdomains, which when disrupted may result in severe pathological consequences.…”

Early events in acute pancreatitis

“…The activation peptides of trypsinogen and carboxypeptidase A 1 (CPA 1 ), which are cleaved from the respective proenzyme during the process of activation, are released into the pancreatic tissue or the serum early in the course of acute pancreatitis [20,[23][24][25][26][27].…”

“…One study that employed the caerulein model of acute pancreatitis reported a biphasic pattern of trypsin activity that reached an early peak after 1 hour and a later second peak after several hours [27]. This observation suggests that more than one mechanism may be involved in the activation of pancreatic zymogens, and the second peak may require the infiltration of inflammatory cells into the pancreas [27]. Taken together, these observations represent compelling evidence that premature, intracellular zymogen activation plays a critical role in initiating acute pancreatitis.…”