Proteolytic Cleavage and Inactivation of a2-Plasmin Inhibitor and C1 Inactivator by Human Polymorphonuclear Leukocyte Elastase

Author(s): Harpel, P.

Journal/Book: The Journal of Biological Chemistry. 1982; 257: 9849-9854.

Abstract: This study has examined the interaction between human leukocyte elastase and ?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 ?2-plasmin inhibitor at two separate sites and generated lower molecular weight fragments similar to those produced by bovine ?-trypsin. C1 inactivator was hydrolyzed at three different regions on the molecule whereas, ?-trypsin cleaved two regions in common with leukocyte elastase.These findings suggest that inactivation of ?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.

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