Influence of the human pancreatic secretory trypsin inhibitor on trypsin-induced C3 and kininogen cleavage: an in vitro study.
Cleavage of C3 and kininogen in human plasma following the addition of increasing amounts of human cationic trypsin was studied using an in vitro model. The cleavage was correlated to the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-proteinase inhibitor, and also with varying amounts of human pancreatic secretory trypsin inhibitor. When alpha 2-macroglobulin reached about 70% saturation, there was a prompt cleavage of most of the C3 and kininogen in spite of the presence of 90% free alpha 1-proteinase inhibitor. The consumption of alpha 1-proteinase inhibitor decreased with increasing concentrations of the pancreatic secretory trypsin inhibitor. This inhibitor was needed in a concentration of about 10 mumol to block trypsin-induced C3 and kininogen cleavage completely. As trypsin is thought to be the key trigger enzyme of the pathophysiological changes in acute pancreatitis, it seems reasonable to propose that the pancreatic secretory trypsin inhibitor might be of therapeutic interest in severe acute pancreatitis provided large enough amounts can be made available.
D003167:Complement Activation / Q000187:drug effects; D003176:Complement C3 / Q000378:metabolism*; D006801:Humans; D007704:Kininogens / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D014357:Trypsin / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000511:alpha-Macroglobulins / Q000378:metabolism
D003176:Complement C3; D007704:Kininogens; D014361:Trypsin Inhibitors; D000511:alpha-Macroglobulins; D014357:Trypsin