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Facilitating roles of murine platelet glycoprotein Ib and αIIbβ3 in phosphatidylserine exposure during vWF–collagen‐induced thrombus formation
Author(s) -
Kuijpers Marijke J. E.,
Schulte Valerie,
Oury Cécile,
Lindhout Theo,
Broers Jos,
Hoylaerts Marc F.,
Nieswandt Bernhard,
Heemskerk Johan W. M.
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.062414
Subject(s) - gpvi , platelet , chemistry , collagen receptor , integrin , von willebrand factor , platelet membrane glycoprotein , thrombus , platelet adhesiveness , phosphatidylserine , microbiology and biotechnology , platelet activation , glycoprotein ib , receptor , immunology , biochemistry , medicine , biology , phospholipid , membrane , platelet aggregation
Vessel wall damage exposes collagen fibres, to which platelets adhere directly via the collagen receptors glycoprotein (GP) VI and integrin α 2 β 1 and indirectly by collagen‐bound von Willebrand factor (vWF) via the GPIb‐V‐IX and integrin αIIbβ3 receptor complexes. Platelet–collagen interaction under shear stimulates thrombus formation in two ways, by integrin‐dependent formation of platelet aggregates and by surface exposure of procoagulant phosphatidylserine (PS). GPVI is involved in both processes, complemented by α2β1. In mouse blood flowing over collagen, we investigated the additional role of platelet–vWF binding via GPIb and αIIbβ3. Inhibition of GPIb as well as blocking of vWF binding to collagen reduced stable platelet adhesion at high shear rate. This was accompanied by delayed platelet Ca 2+ responses and reduced PS exposure, while microaggregates were still formed. Inhibition of integrin αIIbβ3 with JON/A antibody, which blocks αIIbβ3 binding to both vWF and fibrinogen, reduced PS exposure and aggregate formation. The JON/A effects were not enhanced by combined blocking of GPIb–vWF binding, suggesting a function for αIIbβ3 downstream of GPIb. Typically, with blood from FcR γ‐chain +/− mutant mice, expressing 50% of normal platelet GPVI levels, GPIb blockage almost completely abolished platelet adhesion and PS exposure. Together, these data indicate that, under physiological conditions of flow, both adhesive receptors GPIb and αIIbβ3 facilitate GPVI‐mediated PS exposure by stabilizing platelet binding to collagen. Hence, these glycoproteins have an assistant procoagulant role in collagen‐dependent thrombus formation, which is most prominent at reduced GPVI activity and is independent of the presence of thrombin.