title: Severe acute pancreatitis and reduced acinar cell apoptosis in the exocrine pancreas of mice deficient for the Cx32 gene.
abstract: OBJECTIVE
  The early events leading to acinar cell injury during acute pancreatitis are poorly characterized. Signaling through gap junction channels contributes to the homeostasis of the exocrine pancreas by coordinating acinar cell activity within an acinus. To explore the role of gap junctional communication in acinar cell response to injury, we analyzed the course of acute pancreatitis induced by injection of cerulein in mice deficient for Cx32, the major gap junction protein expressed in the exocrine pancreas.
  
  
  METHODS
  The severity of pancreatitis was evidenced by measuring serum amylase activity, pancreatic edema, acinar cell necrosis, pancreatic tumor necrosis factor alpha concentration, and myeloperoxidase activity. Acinar cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL), caspase-3 activity, and Bax/Bcl-2 expression. Expression and function of connexin were evaluated by immunofluorescence and dye coupling.
  
  
  RESULTS
  Cx32-deficient mice exhibited a deleterious course of acute pancreatitis with increased necrosis, edema, and inflammation of the exocrine pancreas. In addition, the exocrine pancreas of Cx32-deficient mice showed a decreased number of TUNEL-positive acinar cells and decreased caspase-3 activity but no change in Bax or Bcl-2 pancreatic expression. Interestingly, chemicals known to induce apoptosis in vivo had no effect on Cx32-deficient pancreatic acinar cells.
  
  
  CONCLUSIONS
  Deficiency of a pancreatic connexin converts a mild reversible form of acute pancreatitis into a severe disease and decreases the sensitivity of acinar cells to apoptotic stimuli. The results show that acinar cell-to-cell communication plays a key role in the modulation of severity of acute pancreatitis.
authors.affiliation: Divisions of Gastroenterology, University Hospitals, Geneva, Switzerland.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Frossard
authors.forename: Laura
authors.initials: L
authors.lastname: Rubbia-Brandt
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wallig
authors.forename: Messod
authors.initials: M
authors.lastname: Benathan
authors.forename: Thomas
authors.initials: T
authors.lastname: Ott
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: Antoine
authors.initials: A
authors.lastname: Hadengue
authors.forename: Susanne
authors.initials: S
authors.lastname: Suter
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Marc
authors.initials: M
authors.lastname: Chanson
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002108:Ceruletide; D017630:Connexins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D010179:Pancreas / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012720:Severity of Illness Index; D051028:bcl-2-Associated X Protein; D000097002:Gap Junction beta-1 Protein
chemical_list: D002108:Ceruletide; D017630:Connexins; D005978:Glutathione; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000097002:Gap Junction beta-1 Protein; C494827:Bax protein, mouse