Proteolytic cleavage and inactivation of alpha 2-plasmin inhibitor and C1 inactivator by human polymorphonuclear leukocyte elastase.
This study has examined the interaction between human leukocyte elastase and alpha 2-plasmin inhibitor, or C1 inactivator, inhibitors of proteases of the complement, kinin, coagulation, and fibrinolytic enzyme systems. Leukocyte elastase, in catalytic concentrations, progressively inactivates the plasmin inhibitory activity of both inhibitors. The C1s binding function of C1 inactivator is also destroyed by leukocyte elastase. The nature of the molecular events underlying the inactivation of these protease inhibitors was examined by acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Loss of functional activity was accompanied by limited proteolytic cleavage of both inhibitors with the production of several characteristic derivative peptide chains. Leukocyte elastase cleaved alpha 2-plasmin inhibitor at two separate sites and generated lower molecular weight fragments similar to those produced by bovine beta-trypsin. C1 inactivator was hydrolyzed at three different regions on the molecule whereas beta-trypsin cleaved two regions in common with leukocyte elastase. These findings suggest that inactivation of alpha 2-plasmin inhibitor and C1 inactivator by leukocyte elastase released in the inflammatory reaction may potentiate pathological proteolysis. The limited digestion of these inhibitory proteins by leukocyte elastase may prove useful in studies of their primary structure.
D003166:Complement Activating Enzymes / Q000378:metabolism; D003174:Complement C1 Inactivator Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003173:Complement C1s; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008970:Molecular Weight; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D014357:Trypsin; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D003174:Complement C1 Inactivator Proteins; D000979:alpha-2-Antiplasmin; D003166:Complement Activating Enzymes; D010196:Pancreatic Elastase; D014357:Trypsin; D003173:Complement C1s