Asialo von Willebrand factor interactions with platelets. Interdependence of glycoproteins Ib and IIb/IIIa for binding and aggregation.

Abstract

Asialo von Willebrand factor (AS-vWf) binds to and aggregates normal human platelets in the absence of ristocetin. Maximal specific binding of AS-vWf is 1-2 micrograms vWf protein/10(8) platelets. Despite the specificity of the binding, only 60% of the bound AS-vWf can be dissociated after equilibrium has been reached. We investigated the site of binding and the mechanism of aggregation of platelets by AS-vWf by (a) pre-incubating platelets with either of two monoclonal antibodies, one against glycoprotein Ib (GPIb) or a second against the glycoprotein IIb/IIIa complex (GPIIb/IIIa), and (b) varying the concentration of fibrinogen in the medium. The results of our studies indicate that AS-vWf binds initially to GPIb. This binding then results in the exposure of receptors for AS-vWf on GPIIb/IIIa. In the presence of plasma fibrinogen, both AS-vWf and fibrinogen bind to GPIIb/IIIa. In the presence of plasma fibrinogen, 50% more AS-vWf binds to the platelet, and this additional AS-vWf binds almost exclusively to GPIIb/IIIa. Despite this enhanced binding of AS-vWf in the absence of fibrinogen, platelet aggregation is much less than that which occurs in the presence of plasma fibrinogen. Comparative studies of AS-vWf binding to normal platelets and the platelets of patients with Glanzmann's thrombasthenia reveal decreased binding to the thrombasthenic platelets and a marked decrease in the extent of platelet aggregation. These studies indicate that AS-vWf binding to, and ensuing aggregation of, platelets is different from that observed with intact vWf protein when platelets are stimulated with either ristocetin or thrombin. The AS-vWf binds to GPIb which, in turn, makes additional AS-vWf receptors available on GPIIb/IIIa. If plasma fibrinogen is present, it competes with the AS-vWf for binding to GPIIb/IIIa and causes aggregation of platelets. In the presence of plasma fibrinogen, more of the AS-vWf binds to GPIIb/IIIa, but this AS-vWf is much less effective than fibrinogen in supporting platelet aggregation.

• Authors: H R Grainick, S B Williams, B S Coller
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 75 Issue 1 Pg. 19-25 (Jan 1985) ISSN: 0021-9738 [Print] United States
• PMID: 2981249 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Asialoglycoproteins
• Blood Coagulation Factors
• Glycoproteins
• Membrane Proteins
• Platelet Membrane Glycoproteins
• Receptors, Cell Surface
• asialo-von Willebrand Factor
• von Willebrand Factor
• von Willebrand factor receptor

Topics

• Antibodies, Monoclonal
• Asialoglycoproteins
• Blood Coagulation Factors (metabolism)
• Blood Platelets (physiology)
• Glycoproteins (physiology)
• Humans
• Membrane Proteins (physiology)
• Platelet Aggregation
• Platelet Membrane Glycoproteins
• Receptors, Cell Surface (physiology)
• von Willebrand Factor (analogs & derivatives, metabolism)