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Platelet-derived microparticles associate with fibrin during thrombosis
P Siljander1, O Carpen, R Lassila
1Wihuri Research Institute, Helsinki, Finland.
Abstract:
Platelet-derived microparticles (MP) are reported to express both pro- and anticoagulant activities. Nevertheless, their functional significance has remained unresolved. The present study monitored the generation and fate of MP in an experimental model of thrombosis with costimulation of platelets by collagen and thrombin. When minimally anticoagulated (0.5 micromol/L PPACK) blood was perfused over immobilized fibrillar type I collagen in a flow chamber at a low shear rate (300 s(-1)), endogenous thrombin was generated, as evidenced by thrombin-antithrombin III complex. In contrast to full anticoagulation 150 micromol/L PPACK) and the absence of collagen, large platelet aggregates and fibrin ensued during perfusions over collagen in the presence of thrombin. In these thrombi, MP, defined as GPIIbIIIa- and P-selectin-positive vesicles (<1 micron), were found to align fibrin in immunofluorescence and scanning immunoelectron microscopy. Moreover, in sections of embolectomized thromboemboli from patients GPIIbIIIa- and P-selectin-positive material compatible with MP was detected in a fibrin strand-like pattern. In vitro binding studies showed that MP bound to fibrin and acted there as procoagulants. In summary, we show that MP generated during thrombus formation associate with local fibrin. This adhesive function fibrin could imply a sustained modulatory role for MP in evolving thrombi.
Insights
Platelet-derived microparticles (MP) generated during thrombus formation bind to fibrin. This interaction suggests a role for MP in modulating evolving blood clots.
Area of Science:
- Hematology
- Biochemistry
- Cell Biology
Background:
- Platelet-derived microparticles (MP) exhibit both pro- and anticoagulant properties, but their functional significance in thrombosis is unclear.
- Understanding the role of MP in thrombus formation is crucial for developing targeted antithrombotic therapies.
Purpose of the Study:
- To investigate the generation and fate of MP during experimental thrombosis.
- To determine the interaction of MP with fibrin and their functional consequences within thrombi.
Main Methods:
- Utilized a flow chamber model with minimally anticoagulated blood perfused over collagen to induce thrombosis.
- Characterized MP using immunofluorescence and scanning immunoelectron microscopy, identifying them as GPIIbIIIa- and P-selectin-positive vesicles.
- Analyzed human thromboemboli for MP presence and performed in vitro binding studies.
Main Results:
- MP were generated and found to align with fibrin strands within experimental thrombi.
- Similar MP-associated material was detected in human embolectomized thromboemboli.
- In vitro studies confirmed that MP bind to fibrin and exhibit procoagulant activity at the fibrin-binding site.
Conclusions:
- MP generated during thrombus formation associate with and bind to local fibrin.
- This interaction suggests that MP play a sustained, modulatory role in the development of thrombi.
- MP's procoagulant function on fibrin may contribute to thrombus stabilization and growth.