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

Glycoprotein V (GPV) is a subunit of the platelet GPlb-V-IX receptor for vo n 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 erial occluding thrombi in an intravital thrombosis model and abnormal plat elet interaction with the subendothellum. In vitro, GPV-deficient platelets exhibited defective adhesion to a collagen type I-coated surface under flo w or static conditions. Aggregation studies demonstrated a decreased respon se of the GPV-deficient platelets to collagen, reflected by an increased la g phase and reduced amplitude of aggregation. Responses to adenosine diphos phate, arachidonic acid, and the thromboxane analog U46619 were normal but were enhanced to low thrombin concentrations. The defect of GPV null platel ets made them more sensitive to inhibition by the anti-GPVI monoclonal anti body (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 pla telets. V.3 injected in rats as a bolus decreased the ex vivo collagen aggr egation response without affecting the platelet count. Finally, surface pla smon 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. (C) 2001 by T he American Society of Hematology.