title: Mechanisms of acinar cell injury in acute pancreatitis.
abstract: Acute pancreatitis has many causes, all leading to a common pathway of changes within the pancreatic acinar cell. Key amongst these changes is premature intracellular activation of digestive enzymes but this is also accompanied by the appearance of cytosolic vacuoles, co-localization of digestive and lysosomal enzymes, activation of NF-kappaB, and release of pro-inflammatory cytokines. The exact mechanism responsible for enzyme activation remains the subject of much research effort and not a little debate, however it is clear that all of these changes are triggered by an abnormal, sustained rise in cytosolic calcium concentration, which is itself dependent both on release of calcium from endoplasmic reticulum stores and uptake from the extracellular milieu. Activated enzymes are directly damaging to the acinar cell themselves, but recruitment of circulating neutrophils leads to further cellular damage. Cytokines and neutrophil activation are also responsible for the systemic inflammatory response typically seen in severe acute pancreatitis.
authors.affiliation: Division of Surgery and Oncology, University of Liverpool, Liverpool L69 3BX, UK. mraraty@liverpool.ac.uk
authors.forename: M G T
authors.initials: MG
authors.lastname: Raraty
authors.forename: J A
authors.initials: JA
authors.lastname: Murphy
authors.forename: E
authors.initials: E
authors.lastname: Mcloughlin
authors.forename: D
authors.initials: D
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Criddle
authors.forename: R
authors.initials: R
authors.lastname: Sutton
mesh_terms: D000208:Acute Disease; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002766:Cholecystokinin / Q000502:physiology; D003600:Cytosol / Q000737:chemistry; D006801:Humans; D009336:Necrosis; D020556:Neutrophil Infiltration; D010179:Pancreas / Q000166:cytology* / Q000201:enzymology; D010195:Pancreatitis / Q000473:pathology* / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology
chemical_list: D002766:Cholecystokinin; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium