An elastase-dependent pathway of plasminogen activation.
In reaction mixtures containing Glu-plasminogen, alpha 2-antiplasmin, and tissue plasminogen activator or urokinase, either pancreatic or leukocyte elastase enhances the rate of plasminogen activation by 2 or more orders of magnitude. This effect is the consequence of several reactions. (a) In concentrations on the order of 100 nM, elastase degrades plasminogen within 10 min to yield des-kringle1-4-plasminogen (mini-plasminogen), which is 10-fold more efficient than Glu-plasminogen as a substrate for plasminogen activators. Des-kringle1-4-plasminogen is insensitive to cofactor activities of fibrin(ogen) fragments or an endothelial cell cofactor. (b) Des-kringle1-4-plasmin is one-tenth as sensitive as plasmin to inhibition by alpha 2-antiplasmin: k" = 10(6) M-1 s-1 versus 10(7) M-1 s-1. (c) alpha 2-Antiplasmin is disabled efficiently by elastase, with a k" of 20,000 M-1 s-1. The elastase-dependent reactions are not influenced by 6-aminohexanoate. In diluted (10-fold) blood plasma, the capacity of endogenous inhibitors to block plasmin expression is suppressed by 30 microM elastase. It is proposed that elastases provide an alternative pathway for Glu-plasminogen activation and a mechanism for controlling initiation of fibrinolysis by urokinase-type plasminogen activators.
Machovich
R
R
Department of Biochemistry, Mayo Clinic, Rochester, Minnesota 55905.
Owen
W G
WG
D000818:Animals; D005342:Fibrinolysis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010196:Pancreatic Elastase / Q000097:blood / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D010960:Plasminogen Activators; D010196:Pancreatic Elastase; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator