The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis.

The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Research Abstract Details 

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The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Abstract Text:

Wolfgang Bergmeier,Crystal L Piffath,Tobias Goerge,Stephen M Cifuni,Zaverio M Ruggeri,Jerry Ware,Denisa D Wagner,Wolfgang Bergmeier,Crystal L Piffath,Tobias Goerge,Stephen M Cifuni,Zaverio M Ruggeri,Jerry Ware,Denisa D Wagner,

GPIbalpha binding to von Willebrand factor (VWF) exposed at a site of vascular injury is thought to be the first step in the formation of a hemostatic plug. However, our previous studies in VWF-deficient mice demonstrated delayed but not absent arterial thrombus formation, suggesting that, under these conditions, GPIbalpha may bind other ligands or that a receptor other than GPIbalpha can mediate platelet adhesion. Here, we studied thrombus formation in transgenic mice expressing GPIbalpha in which the extracellular domain was replaced by that of the human IL-4 receptor (IL4Ralpha/GPIbalpha-tg mice). Platelet adhesion to ferric chloride-treated mesenteric arterioles in IL4Ralpha/GPIbalpha-tg mice was virtually absent in contrast to avid adhesion in WT mice. As a consequence, arterial thrombus formation was inhibited completely in the mutant mice. Our studies further show that, when infused into WT recipient mice, IL4Ralpha/GPIbalpha-tg platelets or WT platelets lacking the 45-kDa N-terminal domain of GPIbalpha failed to incorporate into growing arterial thrombi, even if the platelets were activated before infusion. Surprisingly, platelets lacking beta3 integrins, which are unable to form thrombi on their own, incorporated efficiently into WT thrombi. Our studies provide in vivo evidence that GPIbalpha absolutely is required for recruitment of platelets to both exposed subendothelium and thrombi under arterial flow conditions. Thus, GPIbalpha contributes to arterial thrombosis by important adhesion mechanisms independent of the binding to VWF.

The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Publishing Authors By Initials

W Bergmeier,CL Piffath,T Goerge,SM Cifuni,ZM Ruggeri,J Ware,DD Wagner,W Bergmeier,CL Piffath,T Goerge,SM Cifuni,ZM Ruggeri,J Ware,DD Wagner,

For similar proteins: blood proteins: blood coagulation factors: von willebrand factor research abstracts see: proteins: blood proteins: blood coagulation factors: von willebrand factor research

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The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 16900-5

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 30

MONTH: 10

YEAR: 2006

The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Keywords Mesh Terms:

KEYWORDS: von Willebrand Factor

MESH TERMS: physiology

Chemical & Substance for Abstract: The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis. Information

Substance Name: von Willebrand Factor

Registry Number: 0

Grant and Affiliation Information for The role of platelet adhesion receptor GPIbalpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis.

AFFILIATION: CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. bergmeier@cbrinstitute.org

Country: United States

AGENCY: United States NHLBI

GRANT: R37 HL 41002

ACRONYM: HL

MEDLINETA: Proc Natl Acad Sci U S A

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