Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation

Glycoprotein V (GPV) is a subunit of the platelet GPIb-V-IX receptor for von Willebrand factor and thrombin. GPV is cleaved from the platelet surface during activation by thrombin, but its role in hemostasis is still unknown. It is reported that GPV knockout mice had a decreased tendency to form art...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2001-08, Vol.98 (4), p.1038-1046
Main Authors: Moog, Sylvie, Mangin, Pierre, Lenain, Nadège, Strassel, Catherine, Ravanat, Catherine, Schuhler, Simone, Freund, Monique, Santer, Martine, Kahn, Mark, Nieswandt, Bernhard, Gachet, Christian, Cazenave, Jean-Pierre, Lanza, François
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - pharmacology
Biological and medical sciences
Blood coagulation. Blood cells
Collagen - metabolism
Disease Models, Animal
Flow Cytometry
Fundamental and applied biological sciences. Psychology
Humans
Mice
Mice, Knockout
Molecular and cellular biology
Platelet
Platelet Adhesiveness - drug effects
Platelet Aggregation - drug effects
Platelet Glycoprotein GPIb-IX Complex - immunology
Platelet Glycoprotein GPIb-IX Complex - metabolism
Platelet Glycoprotein GPIb-IX Complex - pharmacology
Protein Binding
Rats
Surface Plasmon Resonance
Thrombosis - blood
Thrombosis - etiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glycoprotein V (GPV) is a subunit of the platelet GPIb-V-IX receptor for von Willebrand factor and thrombin. GPV is cleaved from the platelet surface during activation by thrombin, but its role in hemostasis is still unknown. It is reported that GPV knockout mice had a decreased tendency to form arterial occluding thrombi in an intravital thrombosis model and abnormal platelet interaction with the subendothelium. In vitro, GPV-deficient platelets exhibited defective adhesion to a collagen type I–coated surface under flow or static conditions. Aggregation studies demonstrated a decreased response of the GPV-deficient platelets to collagen, reflected by an increased lag phase and reduced amplitude of aggregation. Responses to adenosine diphosphate, arachidonic acid, and the thromboxane analog U46619 were normal but were enhanced to low thrombin concentrations. The defect of GPV null platelets made them more sensitive to inhibition by the anti-GPVI monoclonal antibody (mAb) JAQ1, and this was also the case in aspirin- or apyrase-treated platelets. Moreover, an mAb (V.3) against the extracellular domain of human GPV selectively inhibited collagen-induced aggregation in human or rat platelets. V.3 injected in rats as a bolus decreased the ex vivo collagen aggregation response without affecting the platelet count. Finally, surface plasmon resonance studies demonstrated binding of recombinant soluble GPV on a collagen-coupled matrix. In conclusion, GPV binds to collagen and appears to be required for normal platelet responses to this agonist.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V98.4.1038