Mini-plasminogen: a mechanism for leukocyte modulation of plasminogen activation by urokinase.
Urokinase activation of blood fibrinolysis involves polymorphonuclear leukocytes. To determine if a leukocyte proteinase can modulate plasminogen activation, plasminogen was digested with leukocyte elastase. A major product was a small, approximately 34,000 dalton fragment (mini-plasminogen), without lysine-binding function, but with fibrin-binding activity. After urokinase activation, the resulting mini-plasmin had amidolytic activity for a tripeptide plasmin substrate and fibrinolytic activity. By 125I-fibrin assay, activities of mini-plasmin and plasmin (12 nmole/liter) were 38 and 20 ng fibrin lysed/min, respectively. Lysis times of fibrin clots containing urokinase, and mini-plasminogen or plasminogen (800 nmole/liter), were 282 and 290 sec, respectively. Mini-plasmin and plasmin were inhibited similarly by epsilon-aminocaproic acid and normal plasma, but differed in responses to gel filtration fractions of plasma containing alpha 2-antiplasmin and alpha 2-macroglobulin, the primary and secondary plasmin inhibitors. With purified inhibitors, mini-plasmin required higher concentrations of, or longer preincubation with, alpha 2-antiplasmin, and lower concentrations of, or shorter preincubation with, alpha 2-macroglobulin, to produce inhibition equivalent to that observed with plasmin. Leukocyte elastase digests plasminogen to generate a mini-plasminogen which, when activated by urokinase, has a novel pattern of response to the major plasmin inhibitors in plasma.
D000614:Aminocaproates / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010958:Plasminogen / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000614:Aminocaproates; D004791:Enzyme Inhibitors; D010958:Plasminogen; D010450:Endopeptidases; D010196:Pancreatic Elastase; D014568:Urokinase-Type Plasminogen Activator