Document Detail


Interstitial trypsinogen release and its relevance to the transformation of mild into necrotizing pancreatitis in rats.
MedLine Citation:
PMID:  10464149     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Intracellular activation of trypsinogen is currently believed to initiate pancreatitis. Factors responsible for the progression of mild to necrotizing pancreatitis are poorly understood. This study evaluated the significance of interstitial protease release and activation in this process. METHODS: In rats with cerulein-induced pancreatitis, concentrations of trypsinogen and its activation peptide TAP were measured in lymph and blood, and pancreatic injury was determined. Activation of extracellular trypsinogen was induced by intravenous infusion of enterokinase, which does not enter the acinar cell. Gabexate mesilate (acinar cell permeable) or soybean trypsin inhibitor (acinar cell nonpermeable) was administered to distinguish the effects of intracellular or extracellular protease activation. RESULTS: In cerulein pancreatitis, trypsinogen levels increased prominently and were highest in lymph and portal vein blood, whereas TAP increments were modest. Combined cerulein/enterokinase infusions resulted in marked TAP increases in lymph and blood and in severe necrohemorrhagic pancreatitis. Gabexate mesilate as well as soybean trypsin inhibitor significantly decreased TAP levels in both lymph and blood and reduced pancreatic injury, with no significant differences between groups. CONCLUSIONS: In secretagogue-induced pancreatitis, large amounts of trypsinogen are present in the interstitium and drain via the portal and lymphatic circulation. Activation of this extracellular trypsinogen induces hemorrhagic necrosis in a setting of mild edematous pancreatitis. This phenomenon may be the central event in the progression to fulminant necrotizing pancreatitis.
Authors:
W Hartwig; R E Jimenez; J Werner; K B Lewandrowski; A L Warshaw; C Fernández-del Castillo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gastroenterology     Volume:  117     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-09-16     Completed Date:  1999-09-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  717-25     Citation Subset:  AIM; IM    
Affiliation:
Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA. fernandez-delcastillo.carlos@mgh.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Caerulein / pharmacology
Enteropeptidase / pharmacology
Enzyme-Linked Immunosorbent Assay
Male
Oligopeptides / metabolism
Pancreatitis / pathology,  physiopathology*
Pancreatitis, Acute Necrotizing / metabolism*,  pathology
Rats
Rats, Sprague-Dawley
Trypsinogen / metabolism*
Chemical
Reg. No./Substance:
0/Oligopeptides; 0/trypsinogen activation peptide; 17650-98-5/Caerulein; 9002-08-8/Trypsinogen; EC 3.4.21.9/Enteropeptidase
Comments/Corrections
Comment In:
Gastroenterology. 2000 Feb;118(2):452   [PMID:  10691375 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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