Interaction of asialo von Willebrand factor with glycoprotein Ib induces fibrinogen binding to the glycoprotein IIb/IIIa complex and mediates platelet aggregation

Journal Article · Mon Apr 01 04:00:00 EST 1985 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI111816· OSTI ID:5126419

De Marco, L; Girolami, A; Russell, S; Ruggeri, Z M

Von Willebrand factor (vWF) is necessary for the initial attachment of platelets to exposed subendothelium, particularly under flow conditions like those prevailing in the microcirculation. Little is known about its possible participation in subsequent events leading to formation of platelet thrombi at sites of vascular injury. The authors addressed this question by studying the mechanisms by which desialylated vWF induces platelet aggregation in the absence of any other stimulus. Asialo vWF, unlike the native molecule, does not require ristocetin to interact with platelets. They have shown here that binding of asialo vWF to platelets was accompanied by release of dense granule content and subsequent ADP-dependent fibrinogen binding to receptors on the glycoprotein (GP) IIb/IIIa complex. The initial interaction of asialo vWF with platelets was mediated by GPIb, as shown by blocking obtained with monoclonal antibody. Inhibition of this initial interaction completely abolished platelet aggregation induced by asialo vWF. This, however, did not block asialo vWF binding to platelets, but rather inhibited subsequent fibrinogen binding induced by asialo vWF. Therefore, the latter process was also essential for platelet aggregation under the conditions described. This study shows that asialo, and possibly native, vWF acts as a platelet agonist after its binding to GPIb and induces aggregation through a pathway dependent on GPIIb/IIIa-related receptors.

• Research Organization: Centro Immunotrasfusionale, Pordenone, Italy
• OSTI ID: 5126419
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 4; ISSN JCINA
• Country of Publication: United States
• Language: English

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550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
AGGLOMERATION
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BLOOD PLATELETS
BODY FLUIDS
CARBOHYDRATES
CELL CONSTITUENTS
CELL MEMBRANES
COAGULANTS
CONFIGURATION INTERACTION
DRUGS
FIBRINOGEN
GLOBULINS
GLUCOPROTEINS
HEMATOLOGIC AGENTS
HEMOSTATICS
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MATERIALS
MEMBRANES
ORGANIC COMPOUNDS
PROTEINS
SACCHARIDES
TRACER TECHNIQUES