On the potential role of trypsin and trypsin inhibitors in acute pancreatitis.
The protective role of alpha 2-macroglobulin, alpha 1-antitrypsin and Aprotinin against trypsin-induced effects on C3 and kininogen was studied in a human in vitro model. When human cationic trypsin was added to human serum or plasma, there was a gradual saturation of alpha 2-macroglobulin and later of alpha 1-antitrypsin. When alpha 2-macroglobulin was 70% saturated, there was a prompt cleavage of both C3 and kininogen, in spite of 80% free and active alpha 1-antitrypsin. These biochemical changes and antiprotease levels are identical to our findings in patients with acute pancreatitis, especially in their peritoneal exudate. Very high concentrations of Aprotinin, 5-15 times higher than ever used clinically, blocked the cleavage of both C3 and kininogen, while doses commonly used clinically were without significant effect. The clinical implications are: A trypsin-induced activation of both the complement and kinin system with clinical consequence is possible in patients with acute pancreatitis because of very low alpha 2-macroglobulin levels. Aprotinin in adequate doses, 5-15 times higher than ever used clinically, seems to protect against activation of two systems.
D000208:Acute Disease; D001798:Blood Proteins / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007700:Kinetics; D010196:Pancreatic Elastase / Q000097:blood; D010195:Pancreatitis / Q000503:physiopathology*; D014357:Trypsin / Q000097:blood*; D014361:Trypsin Inhibitors / Q000378:metabolism*; D014362:Trypsinogen / Q000097:blood; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins / Q000378:metabolism
D001798:Blood Proteins; D003176:Complement C3; D014361:Trypsin Inhibitors; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D014362:Trypsinogen; D010196:Pancreatic Elastase; D014357:Trypsin