Interaction of porcine von Willebrand factor with the platelet glycoproteins Ib and IIb/IIIa complex.
Porcine von Willebrand factor (PvWF) induces platelet aggregation which is thought to be responsible for the thrombocytopenia that occurs in haemophilic patients treated with commercial preparations of porcine factor VIII. This study demonstrates that such aggregation can be completely inhibited by a monoclonal antibody against human platelet glycoprotein GPIb and partially inhibited by an antibody directed against platelet GPIIb/IIIa. The interaction of PvWF with GPIb is also demonstrated by the inhibitory effect of purified glycocalycin on aggregation. The binding site of PvWF to GPIb is very close to that of human vWF, since a recombinant peptide blocks the binding of both molecules to GPIb. When platelets are incubated with PvWF, the GPIIb/IIIa receptor is activated and binds fibrinogen. PvWF also binds to GPIIb/IIIa when platelets are stimulated with thrombin, suggesting that the molecule has the same RGD sequence as other adhesive proteins (human vWF, fibrinogen, fibronectin and vitronectin). These findings identify the dual mechanisms responsible for in vivo platelet aggregation induced by PvWF, i.e. binding to GPIb and activation of the GPIIb/IIIa receptor.
Pareti
F I
FI
Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, IRCCS Maggiore Hospital, Pordenone, Italy.
Mazzucato
M
M
Bottini
E
E
Mannucci
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D002847:Chromatography, Agarose; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D013552:Swine; D014841:von Willebrand Factor / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D005340:Fibrinogen