Mouse podoplanin supports adhesion and aggregation of platelets under arterial shear: a novel mechanism of haemostasis

Lombard, S. E., Pollitt, A. Y. ORCID: https://orcid.org/0000-0001-8706-5154, Hughes, C. E. ORCID: https://orcid.org/0000-0002-9790-5820, Di, Y., Mckinnon, T., O'Callaghan, C. A. and Watson, S. P. (2018) Mouse podoplanin supports adhesion and aggregation of platelets under arterial shear: a novel mechanism of haemostasis. Platelets, 29 (7). pp. 716-722. ISSN 0953-7104 doi: 10.1080/09537104.2017.1356919

Abstract/Summary

The Podoplanin-CLEC-2 axis is critical in mice for prevention of haemorrhage in the cerebral vasculature during mid-gestation. This raises the question as to how platelets are captured by podoplanin on neuroepithelial cells in a high shear environment. In this study, we demonstrate that mouse platelets form stable aggregates on mouse podoplanin at arterial shear through a CLEC-2 and Src kinase-dependent pathway. Adhesion and aggregation are also dependent on the platelet glycoprotein (GP) receptors, integrin αIIbβ3 and GPIb, and the feedback agonists ADP and thromboxane A2 (TxA2). CLEC-2 does not bind to von Willebrand factor (VWF) suggesting that the interaction with podoplanin is sufficient to both tether and activate platelets. Consistent with this, surface plasmon resonance measurements reveal that mouse CLEC-2 binds to mouse podoplanin with nanomolar affinity. The present findings demonstrate a novel pathway of haemostasis in which podoplanin supporting platelet capture and activation at arteriolar rates of shear.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/71188
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Taylor & Francis
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