McCarty, O. J. T., Calaminus, S. D. J., Berndt, M. C., Machesky, L. M. and Watson, S. P. (2006) von Willebrand factor mediates platelet spreading through glycoprotein Ib and αIIbβ3 in the presence of botrocetin and ristocetin, respectively. Journal of Thrombosis and Haemostasis, 4(6), pp. 1367-1378. (doi: 10.1111/j.1538-7836.2006.01966.x) (PMID:16706984)
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Abstract
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 αIIbβ3. Objective: To evaluate the ability of GPIb and αIIbβ3 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, VWF stimulates 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 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 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 VWF–GPIb interactions in the context of platelet regulation.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Machesky, Professor Laura |
| Authors: | McCarty, O. J. T., Calaminus, S. D. J., Berndt, M. C., Machesky, L. M., and Watson, S. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of Thrombosis and Haemostasis |
| Publisher: | Wiley |
| ISSN: | 1538-7933 |
| ISSN (Online): | 1538-7836 |
| Published Online: | 17 May 2006 |
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