Cathepsin B activates human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B.
OBJECTIVE
Activation of trypsinogen to trypsin is a crucial step in the development of acute pancreatitis. The cause of this activation is not known although suggested explanations include autoactivation, cathepsin B-mediated activation and activation by mast cell tryptase. The aim of this study was to investigate cathepsin B and tryptase activation of pancreatic zymogens.


METHODS
Trypsinogen-1, proelastase, and procarboxypeptidase B were purified from human pancreatic juice. Human cathepsin B and betaI-tryptase are commercial products. Activation and degradation of zymogens were measured by activity towards specific substrates for trypsin and pancreatic elastase, ELISAs for procarboxypeptidase B and its activation peptide, and a radioimmunoassay for the trypsinogen activation peptide.


RESULTS
Cathepsin B caused activation of trypsinogen-1 with a trypsin yield of about 30% of that produced by enterokinase. Proelastase and procarboxypeptidase B was not activated by cathepsin B. None of the zymogens were inactivated by cathepsin B. Neither monomeric nor tetrameric tryptase could activate any of the examined zymogens.


CONCLUSIONS
Cathepsin B is a competent activator of trypsinogen-1, although not as efficient as enterokinase. If cathepsin B is to play a role in protease activation in acute pancreatitis, this most probably occurs by activation of trypsinogen.
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden. Bjorn.Lindkvist@kir.mas.lu.se
Björn
B
Lindkvist
Ignacio
I
Fajardo
Gunnar
G
Pejler
Anders
A
Borgström
D043424:Carboxypeptidase B / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D014357:Trypsin; D014362:Trypsinogen / Q000378:metabolism*; D053802:Tryptases
D004792:Enzyme Precursors; D014362:Trypsinogen; D043424:Carboxypeptidase B; D012697:Serine Endopeptidases; C022443:proelastase; D010196:Pancreatic Elastase; C489303:PRSS1 protein, human; D014357:Trypsin; D053802:Tryptases; D002401:Cathepsin B