1993
DOI: 10.1055/s-0038-1651640
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Transmembrane Calcium Influx Associated with von Willebrand Factor Binding to GP Ib in the Initiation of Shear-Induced Platelet Aggregation

Abstract: SummaryWe found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two-to three-fold increase in their intracellular concentration ([Ca2+]i). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significa… Show more

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Cited by 173 publications
(113 citation statements)
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“…Of interest is the fact, not documented here, that inhibitors of platelet activation, like prostaglandin E 1 , can indeed prevent shear-induced vWF binding, 2 providing additional evidence in support of a dual receptor mechanisms where the function of one is linked to a response initiated by the other. This is also consistent with the observation that vWF interaction with GP Ib under shear leads to a transmembrane flux of calcium ions that precedes and is independent of an interaction with GP IIb-IIIa (10,11). This hypothetical mechanism of shear-dependent vWF binding to platelets poses some key questions that our present results begin to address.…”
Section: Discussionsupporting
confidence: 91%
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“…Of interest is the fact, not documented here, that inhibitors of platelet activation, like prostaglandin E 1 , can indeed prevent shear-induced vWF binding, 2 providing additional evidence in support of a dual receptor mechanisms where the function of one is linked to a response initiated by the other. This is also consistent with the observation that vWF interaction with GP Ib under shear leads to a transmembrane flux of calcium ions that precedes and is independent of an interaction with GP IIb-IIIa (10,11). This hypothetical mechanism of shear-dependent vWF binding to platelets poses some key questions that our present results begin to address.…”
Section: Discussionsupporting
confidence: 91%
“…This antibody selectively inhibits vWF binding to GP IIb-IIIa as well as platelet aggregation and thrombus formation under high shear conditions (9,26). NMC-4 (IgG1) reacts with the A1 domain of vWF including the disulfide bond between residues Cys 509 and Cys 695 (29,30) and blocks the interaction between vWF and GP Ib under all the experimental conditions tested; it also inhibits shearinduced platelet aggregation (11,31). LJ-229 (IgG1) reacts with a COOH-terminal domain of vWF present in the dimeric fragment II (residues 1366 -2050 of the mature vWF subunit) generated by Staphylococcus aureus V8 protease (32,33); it has no known inhibitory activity on vWF function.…”
Section: Measurement Of Fitc-labeled Vwf Binding To Plateletsmentioning
confidence: 99%
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“…At physiologic shear rates, both GPIb/V/IX and the integrin α IIb β 3 participate in forming intercellular tethers among platelets, leading to the formation of stable platelet aggregates (6). The binding of vWF to GPIb also induces platelet activation, as demonstrated by intracellular calcium mobilization, and leads to the activation of the integrin α IIb β 3 on the platelet surface (7,8). After this first adhesion step, receptor-ligand interactions synergistically promote stable platelet adhesion.…”
Section: Introductionmentioning
confidence: 99%
“…Vascular endothelial cell injury leads to an attenuation of antithrombogenicity as well as the promotion of thrombogenicity. Vascular endothelial cell dysfunctionrelated arterial thrombosis is often linked to platelet activation caused by shear stress (29) and/or miscellanneous platelet agonists (30)(31)(32)(33)(34)(35), and von Willebrand's factor plays a pivotal role in arterial thrombosis (36). In contrast, deep vein thrombosis is based on fibrin thrombi linked to a slow venous blood flow, elevated blood coagulability, and raised platelet aggregability, which are commonly accompanied by activation of the coagulation-fibrinolytic system (14).…”
Section: Discussionmentioning
confidence: 99%