Abstract
Binding of components of the fibrinolytic system to fibrin is important for the regulation of fibrinolysis. In this study, decomposition of the fibrin network and binding of plasminogen and plasminogen activators (PAs) to fibrin during lysis of a plasma clot were investigated with confocal microscopy using fluorescein-labeled preparations of fibrinogen, plasminogen, tissue-type PA (t-PA), and two-chain urokinase-type PA (tcu-PA). Lysis induced by PAs present throughout the plasma clot was accompanied by a gradual loss of fibrin content of fibers and by accumulation of plasminogen onto the fibers. Two sequential phases could be distinguished: a phase of prelysis, during which the fibrin network remained immobile, and a phase of final lysis, during which fibers moved with a tendency to shrink and eventually disappeared. The two phases occurred simultaneously but in different locations when lysis was induced by PAs present in the plasma surrounding the clot. The zone of final lysis was located within a 5-8 microns superficial layer, where fibers were mobile, a surface-associated fibrin agglomerates appeared. Plasminogen accumulated in these agglomerates up to 30-fold as compared with its concentration in the outer plasma. t-PA was also highly concentrated in the agglomerates, and tcu-PA bound to them slightly. The zone of prelysis, where plasminogen was moderately accumulated on the immobile fibers, was located deeper in the clot. This zone was much thinner in the case of t-PA-induced lysis than in the case of tcu-PA-induced lysis, reflecting the difference in penetration of the two PAs into the clot. We conclude that under conditions of diffusional transport of fibrinolytic enzymes from outside a plasma clot, extensive lysis is spatially restricted to a zone not exceeding 5-8 microns from the clot surface. In this zone the structure of the fibrin network undergoes significant changes, and strikingly high accumulation of fibrinolytic components takes place.
Highlights
Binding of components of the fibrinolytic system to fibrin is important for the regulation of fibrinolysis
Decomposition of the fibrin network and binding of plasminogen and plasminogen activators (PAs) to fibrin during lysis of a plasma clot were investigated with confocal microscopy using fluorescein-labeled preparations of fibrinogen, plasminogen, tissuetype PA (t-PA), and two-chain urokinase-type PA
Two different experimental setups were used: 1) lysis induced by a PA present throughout the plasma clot, and 2) lysis induced by a PA added to plasma surrounding the clot
Summary
Binding of components of the fibrinolytic system to fibrin is important for the regulation of fibrinolysis. The zone of final lysis was located within a 5– 8-m superficial layer, where fibers were mobile, and surface-associated fibrin agglomerates appeared Plasminogen accumulated in these agglomerates up to 30-fold as compared with its concentration in the outer plasma. We conclude that under conditions of diffusional transport of fibrinolytic enzymes from outside a plasma clot, extensive lysis is spatially restricted to a zone not exceeding 5– 8 m from the clot surface In this zone the structure of the fibrin network undergoes significant changes, and strikingly high accumulation of fibrinolytic components takes place. Fibrin plays a much more complicated role than that of a mere insoluble substrate for proteolysis It is involved in numerous interactions with components of both fibrinolytic (4 –9) and antifibrinolytic [10, 11] systems, actively participating in the regulation of the self-destruction
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