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 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. (Blood. 2001;98:1038-1046)
Moog
S
S
INSERM U.311, Etablissement Français du Sang-Alsace, Strasbourg, France.
Mangin
P
P
Lenain
N
N
Strassel
C
C
Ravanat
C
C
Schuhler
S
S
Freund
M
M
Santer
M
M
Kahn
M
M
Nieswandt
B
B
Gachet
C
C
Cazenave
J P
JP
Lanza
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D020349:Surface Plasmon Resonance; D013927:Thrombosis / Q000097:blood / Q000209:etiology
D000911:Antibodies, Monoclonal; D019038:Platelet Glycoprotein GPIb-IX Complex; D003094:Collagen