Respective roles of Glycoprotein VI and FcgammaRIIA in the regulation of alphaIIbbeta3-mediated platelet activation to fibrinogen, thrombus buildup, and stability
Abstract
Background: The interplay between platelets and fibrinogen is the cornerstone of thrombus formation. Integrin alphaIIbbeta3 is the main platelet adhesion receptor for fibrinogen and mediates an outside-in signal upon ligand binding that reinforces platelet activation. In addition, FcgammaRIIA 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 FcgammaRIIA 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 FcgammaRIIA and GPVI to thrombus growth and stability. Results: We first confirmed that integrin alphaIIbbeta3 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 FcgammaRIIA, 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 FcgammaRIIA 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 FcgammaRIIA, induces platelet activation and spreading on fibrinogen, and promotes thrombus buildup and stability.
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BibTeX
@article{ahmed2026respective,
title = {{Respective roles of Glycoprotein VI and FcgammaRIIA in the regulation of alphaIIbbeta3-mediated platelet activation to fibrinogen, thrombus buildup, and stability}},
author = {Muhammad Usman Ahmed and Nicolas Receveur and Emily Janus-Bell and Clarisse Mouriaux and Christian Gachet and Martine Jandrot-Perrus and Beatrice Hechler and Elizabeth E. Gardiner and Pierre Mangin},
journal = {Research and Practice in Thrombosis and Haemostasis},
year = {2026},
month = oct,
doi = {10.1002/rth2.12551},
url = {https://univoak.hal.science/hal-05254033v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Respective roles of Glycoprotein VI and FcgammaRIIA in the regulation of alphaIIbbeta3-mediated platelet activation to fibrinogen, thrombus buildup, and stability
AU - Muhammad Usman Ahmed
AU - Nicolas Receveur
AU - Emily Janus-Bell
AU - Clarisse Mouriaux
AU - Christian Gachet
AU - Martine Jandrot-Perrus
AU - Beatrice Hechler
AU - Elizabeth E. Gardiner
AU - Pierre Mangin
PY - 2026
DA - 2026/10/14
JO - Research and Practice in Thrombosis and Haemostasis
DO - 10.1002/rth2.12551
UR - https://univoak.hal.science/hal-05254033v1
AB - Background: The interplay between platelets and fibrinogen is the cornerstone of thrombus formation. Integrin alphaIIbbeta3 is the main platelet adhesion receptor for fibrinogen and mediates an outside-in signal upon ligand binding that reinforces platelet activation. In addition, FcgammaRIIA 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 FcgammaRIIA 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 FcgammaRIIA and GPVI to thrombus growth and stability. Results: We first confirmed that integrin alphaIIbbeta3 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 FcgammaRIIA, 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 FcgammaRIIA 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 FcgammaRIIA, induces platelet activation and spreading on fibrinogen, and promotes thrombus buildup and stability.
SN - 2475-0379
SN - 2475-0379
ER -