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Platelet-derived microparticles associate with fibrin during thrombosis
P Siljander, O Carpen and R Lassila
Wihuri Research Institute, Helsinki, Finland.
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.
Volume 87,
Issue 11,
pp. 4651-4663,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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