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von Willebrand factor mediates platelet spreading through glycoprotein Ib and α IIb β 3 in the presence of botrocetin and ristocetin, respectively
Author(s) -
MCCARTY O. J. T.,
CALAMINUS S. D. J.,
BERNDT M. C.,
MACHESKY L. M.,
WATSON S. P.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.01966.x
Subject(s) - lamellipodium , ristocetin , von willebrand factor , platelet , platelet membrane glycoprotein , glycoprotein ib , chemistry , microbiology and biotechnology , adenosine diphosphate , thromboxane a2 , platelet adhesiveness , cytoskeleton , biochemistry , glycoprotein , receptor , biology , immunology , platelet aggregation , cell
Summary. Background: von Willebrand factor (VWF) plays a critical role in the process of hemostasis by mediating flow‐dependent adhesion and spreading of platelets on exposed extracellular matrix proteins following vascular injury. To accomplish this, VWF binds to two distinct platelet receptors: glycoprotein (GP)Ib‐IX‐V and integrin α IIb β 3 . Objective: To evaluate the ability of GPIb and α IIb β 3 to mediate platelet adhesion and lamellipodia formation on immobilized VWF in the presence of the biochemical modulators, ristocetin and botrocetin. Results: In the presence of botrocetin and inhibitors of adenosine diphosphate (ADP) and thromboxane A 2 (TxA 2 ), VWF is able to support formation of lamellipodia through a GPIb‐dependent mechanism that is independent of α IIb β 3 and PI3‐kinase. Lamellipodia formation under these conditions is incomplete. In marked contrast, in the presence of ristocetin, VWF stimulates formation of fully spread lamellipodia through a pathway that is dependent upon α IIb β 3 and PI3‐kinase. Furthermore, α IIb β 3 also supports platelet spreading on VWF alone, but only in the absence of inhibitors of ADP and TxA 2 . The localization of filamentous actin and the Arp2/3 complex in platelets on VWF in the presence of botrocetin and ristocetin are distinct, yielding disparate lamellipodium kinetic signatures. Interestingly, botrocetin significantly enhances platelet adhesion to VWF under flow in whole blood in an α IIb β 3 ‐independent manner, while ristocetin augments washed platelet adhesion and spreading to VWF under flow in an α IIb β 3 ‐dependent manner. Conclusions: These observations demonstrate that VWF is able to induce lamellipodia formation through distinct receptors, and has important consequences for investigation of the role of VWF–GPIb interactions in the context of platelet regulation.