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.
Sequence of formation of molecular forms of plasminogen and plasmin-inhibitor complexes in plasma activated by urokinase or tissue-type plasminogen activator
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S Thorsen, S Müllertz, E Suenson, P Kok; Sequence of formation of molecular forms of plasminogen and plasmin-inhibitor complexes in plasma activated by urokinase or tissue-type plasminogen activator. Biochem J 1 October 1984; 223 (1): 179–187. doi: https://doi.org/10.1042/bj2230179
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