von Willebrand factor mediates platelet spreading through glycoprotein Ib and αIIbβ3 in the presence of botrocetin and ristocetin, respectively

Owen J.T. Mccarty, S. D.J. Calaminus, M. C. Berndt, L. M. Machesky, S. P. Watson

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Background: vonWillebrand factor (VWF) plays a critical role in the process of hemostasis by mediating flowdependent 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 αIIb β3. Objective: To evaluate the ability of GPIb and αIIb β3 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 A2 (TxA2), VWF is able to support formation of lamellipodia through a GPIb-dependent mechanism that is independent of αIIbβ3 and PI3-kinase. Lamellipodia formation under these conditions is incomplete. In marked contrast, in the presence of ristocetin, VWFstimulates formation of fully spread lamellipodia through a pathway that is dependent upon αIIbβ3 and PI3-kinase. Furthermore, αIIbβ3 also supports platelet spreading on VWF alone, but only in the absence of inhibitors of ADP and TxA2. The localization of filamentous actin and theArp2/3 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 αIIbβ3- independent manner, while ristocetin augments washed platelet adhesion and spreading to VWF under flow in an αIIbβ3- 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 VWFGPIb interactions in the context of platelet regulation.

Original languageEnglish (US)
Pages (from-to)1367-1378
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume4
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • GPIb-IX-V
  • Platelet
  • von Willebrand factor
  • αβ

ASJC Scopus subject areas

  • Hematology

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