Enzymatic inactivation of human plasma C1-inhibitor and alpha 1-antichymotrypsin by Pseudomonas aeruginosa proteinase and elastase.
Two major human plasma proteinase inhibitors, C1-inhibitor and alpha 1-antichymotrypsin, were enzymatically inactivated by Pseudomonas aeruginosa elastase and proteinase. Incubation of C1-inhibitor with the Pseudomonas enzymes at inhibitor/enzyme molar ratios of 1000:1 (elastase) or 22:1 (proteinase) resulted in cleavage of the 104 kDa intact inhibitor to an 89 kDa intermediate which retained full inhibitory activity against plasmin and plasma kallikrein. The intermediate was then cleaved to an 83 kDa inactive product. The initial non-inactivating cleavage of C1-inhibitor occurred in a region of the molecule readily accessible to limited proteolysis by both enzymes. The inactivating cleavage, however, occurred more readily with the elastase. alpha 1-Antichymotrypsin was inactivated by P. aeruginosa proteinase and elastase by limited proteolysis at inhibitor/enzyme molar ratios of 14 000:1. The 64 kDa intact inhibitor was cleaved to form an inactive 60 kDa product, and a low molecular mass peptide fragment was observed. No stable enzyme-inhibitor complexes were detected, and no random proteolysis of the inactivated inhibitors was noted, even after prolonged incubation. Catalytic inactivation of C1-inhibitor and alpha 1-antichymotrypsin by P. aeruginosa proteinase and elastase may contribute to the tissue damage and hemorrhagic lesions which occur during pseudomonal infections.
D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008970:Molecular Weight; D010196:Pancreatic Elastase / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D000514:alpha 1-Antichymotrypsin
D003174:Complement C1 Inactivator Proteins; D000514:alpha 1-Antichymotrypsin; D010450:Endopeptidases; D002918:Chymotrypsin; D010196:Pancreatic Elastase