Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor

Jurk, K; Clemetson, KJ; de Groot, PG; Brodde, MF; Steiner, M; Savion, N; Varon, D; Sixma, JJ; Van Aken, H; Kehrel, BE (2003). Thrombospondin-1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor. FASEB journal, 11(17), pp. 1490-2. Bethesda, Md.: Federation of American Societies for Experimental Biology 10.1096/fj.02-0830fje

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Acute thrombotic arterial occlusion is the leading cause of morbidity and mortality in the Western world. Von Willebrand factor is thought to be the only indispensable adhesive substrate to promote thrombus formation in high shear environments. We found that thrombospondin-1, a glycoprotein enriched in arteriosclerotic plaques, might function as an alternative substrate for thrombus formation. Platelets adhered to thrombospondin-1 in a shear dependent manner with an optimum shear as found in stenosed arteries. Adhesion is extremely firm, with no detachment of platelets up to a shear rate of 4000 s(-1). Experiments using platelets from a patient completely lacking von Willebrand factor showed that von Willebrand factor is not involved in platelet binding to thrombospondin-1. Platelet adhesion to thrombospondin-1 is not mediated via beta3-integrins or GPIa. CD36 partially mediates the adhesion of pre-activated platelets. We identified GPIb as high shear adhesion-receptor for thrombospondin-1. Soluble GPIb, as well as antibodies against the GPIb, blocked platelet adhesion almost completely. The new discovered thrombospondin-1-GPIb adhesion axis under arterial shear conditions might be important, not only during thrombus formation but also for pathological processes where other cells bind to the endothelium or subendothelium, including arteriosclerosis, inflammation and tumor metastasis, and a promising therapeutic target.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Clemetson, Kenneth John

ISSN:

0892-6638

ISBN:

12824298

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1096/fj.02-0830fje

PubMed ID:

12824298

Web of Science ID:

000183818000025

URI:

https://boris.unibe.ch/id/eprint/22162 (FactScience: 32162)

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