Sequence of formation of molecular forms of plasminogen and plasmin-inhibitor complexes in plasma activated by urokinase or tissue-type plasminogen activator.
The pathway of plasminogen transformation was studied in plasma, particularly in relation to fibrin formation and the subsequent stimulation of plasminogen activation. Plasminogen was activated by urokinase (low fibrin-affinity) or tissue-type plasminogen activator (high fibrin-affinity). Formation of 125I-labelled free and inhibitor-bound plasminogen derivatives was quantified after their separation by acetic acid/urea/polyacrylamide-gel electrophoresis. In plasma activator converted Glu-plasminogen (residues 1-790) into Glu-plasmin, which was complexed to alpha 2-plasmin inhibitor. When this inhibitor was saturated, Glu-plasmin was autocatalytically converted into Lys-plasmin (residues 77-790). No plasmin-catalysed Lys-plasminogen formation was observed. Upon fibrin formation, activation initially followed the same Glu-plasminogen-into-Glu-plasmin conversion pathway, and stimulation of plasminogen activation was only observed with tissue-type plasminogen activator. In agreement with the emergence of novel effector function, on early plasmin cleavage of fibrin [Suenson, Lützen & Thorsen (1984) Eur. J. Biochem. 140, 513-522] the fibrin-binding of Glu-plasminogen increased when solid-phase fibrin showed evident signs of degradation. This was associated with the formation of considerable amounts of the more easily activatable Lys-plasminogen, most of which was fibrin-bound. At the same time the rate of plasmin formation with urokinase increased over that in unclotted plasma and the rate of plasmin formation with tissue-type plasminogen activator accelerated. Altogether these processes favoured enhanced fibrin degradation. The rates of Lys-plasminogen and plasmin formation abruptly decreased after lysis of fibrin, probably owing to a compromised effector function on further fibrin degradation.
D000933:Antifibrinolytic Agents / Q000378:metabolism*; D001777:Blood Coagulation; D004591:Electrophoresis, Polyacrylamide Gel; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000494:pharmacology*; D013820:Thermolysin / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins / Q000097:blood
D000933:Antifibrinolytic Agents; D046911:Macromolecular Substances; D000979:alpha-2-Antiplasmin; C038528:alpha-2-macroglobulin-thermolysin complex; D000511:alpha-Macroglobulins; C037742:plasmin-plasmin inhibitor complex; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D013820:Thermolysin