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Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo
Author(s) -
Massberg Steffen,
Konrad Ildiko,
Bültmann Andreas,
Schulz Christian,
Münch Götz,
Peluso Mario,
Lorenz Michael,
Schneider Simon,
Besta Felicitas,
Müller Iris,
Hu Bin,
Langer Harald,
Kremmer Elisabeth,
Rudelius Martina,
Heinzmann Ulrich,
Ungerer Martin,
Gawaz Meinrad
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0464fje
Subject(s) - gpvi , platelet , platelet membrane glycoprotein , chemistry , platelet activation , microbiology and biotechnology , thrombus , collagen receptor , platelet adhesiveness , biochemistry , biophysics , receptor , immunology , integrin , biology , medicine , platelet aggregation
Platelet—collagen interactions play a fundamental role in the process of arterial thrombosis. The major platelet collagen receptor is the glycoprotein VI (GPVI). Here, we determined the effects of a soluble dimeric form of GPVI on platelet adhesion in vitro and in vivo. We fused the extracellular domain of GPVI with the human immunoglobulin Fc domain. The soluble dimeric form of GPVI (GPVI‐Fc) specifically bound to immobilized collagen. Binding of GPVI‐Fc to collagen was inhibited competitively by soluble GPVI‐Fc, but not control Fc lacking the external GPVI domain. GPVI‐Fc inhibited the adhesion of CHO cells that stably express human GPVI and of platelets on collagen and attenuated thrombus formation under shear conditions in vitro. To test the effects of GPVI‐Fc in vivo, arterial thrombosis was induced in the mouse carotid artery, and platelet—vessel wall interactions were visualized by intravital fluorescence microscopy. Infusion of GPVI‐Fc but not of control Fc virtually abolished stable arrest and aggregation of platelets following vascular injury. Importantly, GPVI‐Fc but not control Fc, was detected at areas of vascular injury. These findings further substantiate the critical role of the collagen receptor GPVI in the initiation of thrombus formation at sites of vascular injury and identify soluble GPVI as a promising antithrombotic strategy.