The inhibition of human leucocyte elastase and chymotrypsin-like protease by elastatinal and chymostatin

The ability of elastatinal and chymostatin, Protease Inhibitors of microbial origin, to inhibit human leucocyte proteases (EC 3.4.-) was studied. Elastatinal and chymostatin are capable of inhibiting the pancreatic enzymes Elastase and chymotrypsin, respectively. It was found in these studies, with synthetic substrates, that elastatinal is a much weaker inhibitor of human leucocyte Elastase than it is of porcine pancreatic Elastase. Elastatinal caused no inhibition of the activity of human leucocyte chymotrypsin-like Protease. Chymostatin was found to be a powerful inhibitor of human leucocyte chymotrypsin-like Protease. Its affinity to the leucocyte Protease was higher than its affinity to bovine pancreatic alpha-chymotrypsin. Chymsotatin had a weak inhibitory effect on the activity of human leucocyte Elastase. Studies were also carried out on the ability of chymostatin to inhibit the release of 35SO2-4 from rabbit articular cartilage by human leucocyte chymotrypsin-like Protease. Preincubation of the chymostatin with the Protease before the latter was added to the 35SO2-4 -labeled cartilage caused inhibition of proteolysis as measured by 35SO2-4 release. Preincubation of chymostatin with 35SO2-4 -labeled cartilage prior to addition of the human chymotrypsin-like Protease to the tissue also inhibited 35SO2-4 release. However, in the case of preincubation of cartilage with alpha1 -antitrypsin there was no such inhibition. It therefore appeared that chymostatin, unlike alpha1 -antitrypsin, was capable of penetrating the cartilage matrix and exerting its inhibitory effect upon the human leucocyte chymotrypsin-like Protease that was subsequently added to the tissue.