Mini-Plasminogen: A Mechanism for Leukocyte Modulation of Plasminogen Activation by Urokinase

• Published in: Blood 1981-07, Vol.58 (1), p.97-104
• Main Author: Moroz, Leonard A.
• Format: Article
• Language: English
• Subjects: Aminocaproates - pharmacology; Endopeptidases - metabolism; Enzyme Activation; Enzyme Inhibitors; Humans; Leukocytes - enzymology; Pancreatic Elastase - metabolism; Plasminogen - physiology; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V58.1.97.97

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 ϵ-aminocaproic acid and normal plasma, but differed in responses to gel filtration fractions of plasma containing α2-antiplasmin and α2-macroglobulin, the primary and secondary plasmin inhibitors. With purified inhibitors, mini-plasmin required higher concentrations of, or longer preincubation with, α2-antiplasmin, and lower concentrations of, or shorter preincubation with, α2-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.