Human serum α1‐antichymotrypsin is an inhibitor of pancreatic elastases

Abstract

Incubation of human serum α₁‐antichymotrypsin with human pancreatic elastase 2 or porcine pancreatic elastase results in the complete inhibition of each enzyme as determined by spectrophotometric assays. α₁‐Antichymotrypsin reacts much more rapidly with the human than with the porcine enzyme. The inhibitor:enzyme molar ratio, required to obtain full inhibition of enzymatic activity, is equal to 1.25/1 when α₁‐antichymotrypsin reacts with human pancreatic elastase 2 while it is markedly higher with porcine pancreatic elastase (5.5/1). Patterns obtained by SDS/polyacrylamide gel electrophoresis of the reaction products show the formation with both enzymes of an equimolar complex (M_r near 77000) and the release of a fragment migrating as a peptide of M_r near 5000. Moreover a free proteolytically modified form of α₁‐antichymotrypsin, electrophoretically identical with that obtained in the reaction with cathepsin G or bovine chymotrypsin, is produced in the reaction with each elastase but in a much greater amount when α₁‐antichymotrypsin reacts with porcine elastase than with human elastase. As a consequence of our findings, the specificity of α₁‐antichymotrypsin, so far limited to the inhibition of chymotrypsin‐like enzymes from pancreas and leukocyte origin, has to be extended to the two pancreatic elastases investigated in this work. A contribution of α₁‐antichymotrypsin to the regulatory balance between plasma inhibitors and human pancreatic elastase 2 in pancreatic diseases is suggested.