Respective roles of Glycoprotein VI and FcγRIIA in the regulation of αIIbβ3-mediated platelet activation to fibrinogen, thrombus buildup, and stability
Date
2021
Authors
Ahmed, Muhammad Usman
Receveur, Nicolas
Janus-Bell, Emily
Mouriaux, Clarisse
Gachet, Christian
Jandrot-Perrus, Martine
Hechler, Beatrice
Gardiner, Elizabeth
Mangin, Pierre H.
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Wiley-Blackwell Publishing Ltd
Abstract
Background
The interplay between platelets and fibrinogen is the cornerstone of thrombus formation. Integrin αIIbβ3 is the main platelet adhesion receptor for fibrinogen and mediates an outside‐in signal upon ligand binding that reinforces platelet activation. In addition, FcγRIIA and glycoprotein VI (GPVI) contribute to platelet activation on fibrinogen, thereby participating in thrombus growth and stability. To date, the relative importance of these two immunoreceptor tyrosine‐based activation motif‐bearing receptors in these processes remains unknown.
Objective
The aim of this study was to evaluate the relative contributions of FcγRIIA and GPVI to platelet activation on fibrinogen and subsequent thrombus growth and stability.
Methods
We evaluated human and mouse platelet adhesion to fibrinogen in static assays and a flow‐based approach to evaluate the contribution of FcγRIIA and GPVI to thrombus growth and stability.
Results
We first confirmed that integrin αIIbβ3 is the key receptor supporting platelet adhesion and spreading on fibrinogen. Using human platelets treated with pharmacological blocking agents and transgenic mouse platelets expressing human receptors, data indicate that GPVI, but not FcγRIIA, plays a prominent role in platelet activation on fibrinogen. Moreover, using a flow‐based assay, we observed that blockade of GPVI with 1G5, but not FcγRIIA with IV.3, prevents thrombus growth. Finally, we observed that 1G5, but not IV.3, promotes the disaggregation of thrombi formed on collagen in vitro.
Conclusion
This study provides evidence that GPVI, but not FcγRIIA, induces platelet activation and spreading on fibrinogen, and promotes thrombus buildup and stability.
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Research and Practice in Thrombosis and Haemostasis
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Journal article
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Open Access
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Creative Commons Attribution licence
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