title: Ligation-induced acute pancreatitis increases pancreatic circulating trypsinogen activation peptides.
abstract: Ligation of the common bile-pancreatic duct induces hyperamylasemia and acute pancreatitis in rats. Pancreatic morphologic changes include edema, acinar cell damage, and mild inflammation. The pathogenesis of acute pancreatitis in this model is not understood, but may involve altered secretion and intrapancreatic activation of acinar proteases. We hypothesized that trypsinogen activation, measured by the production of plasma and pancreatic trypsinogen activation peptides (TAP), occurs early in this model. We performed the following experiments: rats were prepared with (1) bile-pancreatic ducts ligated and (2) ducts dissected but not ligated (sham). Rats were killed after 6, 24, and 48 hr. Serum amylase was measured and histologic sections were analyzed for morphologic changes. TAP was measured in both serum and pancreatic tissue homogenates using a specific polyclonal. anti-TAP antibody in an enzyme-linked immunosorbant assay. After 6, 24, and 48 hr of bile-pancreatic duct ligation, hyperamylasemia and acute morphologic changes of acute pancreatitis were observed. Evidence of acinar cell destruction was not evident until 48 hr after ligation. Levels of serum and pancreatic tissue TAP were significantly elevated at both 24 and 48 hr after ligation compared to those of sham. We conclude that increased intrapancreatic trypsinogen activation occurs early in this form of experimental acute pancreatitis and that it occurs prior to evidence of acinar cell destruction. These data and observations support the possibility that intrapancreatic protease activation contributes to the pathogenesis of ligation-induced acute pancreatitis.
authors.affiliation: Department of Surgery, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: L T
authors.initials: LT
authors.lastname: Merriam
authors.forename: D
authors.initials: D
authors.lastname: Wilcockson
authors.forename: I
authors.initials: I
authors.lastname: Samuel
authors.forename: R J
authors.initials: RJ
authors.lastname: Joehl
mesh_terms: D000208:Acute Disease; D000818:Animals; D008026:Ligation; D008297:Male; D009842:Oligopeptides / Q000096:biosynthesis*; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014362:Trypsinogen / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; C080396:trypsinogen activation peptide; D014362:Trypsinogen