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CLEC-2 expression is maintained on activated platelets and on platelet microparticles

Gitz, E., Pollitt, A. Y., Gitz-Francois, J. J., Alshehri, O., Mori, J., Montague, S., Nash, G. B., Douglas, M. R., Gardiner, E. E., Andrews, R. K., Buckley, C. D., Harrison, P. and Watson, S. P. (2014) CLEC-2 expression is maintained on activated platelets and on platelet microparticles. Blood, 124 (14). pp. 2262-2270. ISSN 0006-4971

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To link to this item DOI: 10.1182/blood-2014-05-572818

Abstract/Summary

The C-type lectin-like receptor CLEC-2 mediates platelet activation through a hem-immunoreceptor tyrosine-based activation motif (hemITAM). CLEC-2 initiates a Src- and Syk-dependent signaling cascade that is closely related to that of the 2 platelet ITAM receptors: glycoprotein (GP)VI and FcγRIIa. Activation of either of the ITAM receptors induces shedding of GPVI and proteolysis of the ITAM domain in FcγRIIa. In the present study, we generated monoclonal antibodies against human CLEC-2 and used these to measure CLEC-2 expression on resting and stimulated platelets and on other hematopoietic cells. We show that CLEC-2 is restricted to platelets with an average copy number of ∼2000 per cell and that activation of CLEC-2 induces proteolytic cleavage of GPVI and FcγRIIa but not of itself. We further show that CLEC-2 and GPVI are expressed on CD41+ microparticles in megakaryocyte cultures and in platelet-rich plasma, which are predominantly derived from megakaryocytes in healthy donors, whereas microparticles derived from activated platelets only express CLEC-2. Patients with rheumatoid arthritis, an inflammatory disease associated with increased microparticle production, had raised plasma levels of microparticles that expressed CLEC-2 but not GPVI. Thus, CLEC-2, unlike platelet ITAM receptors, is not regulated by proteolysis and can be used to monitor platelet-derived microparticles.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:44791
Publisher:American Society of Hematology

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