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DOI: 10.1055/a-2565-9496
Homophilic Interactions of Platelet F11R/JAM-A with Its Surface-Bound Counterpart Facilitate Thrombus Formation
Funding This work was supported by the National Science Centre grant OPUS (UMO-2020/37/B/NZ3/00301).
Abstract
Background
F11Receptor/junctional adhesion molecule-A (F11R/JAM-A) is a transmembrane protein expressed in endothelial cells, epithelial cells, and in blood platelets. In blood platelets, F11R/JAM-A participates in adhesion under static conditions, suppresses the activation of the platelet αIIbβ3 integrin and was shown to activate blood platelets as soluble form via homophilic interactions.
Objectives
The purpose of presented study was to evaluate whether F11R/JAM-A is involved in platelet adhesion under flow conditions and in thrombus formation.
Methods
F11R/JAM-A contribution to platelet adhesion under flow conditions was assessed using flow chamber assay. Monoclonal antibodies and recombinant F11R/ JAM-A were used to assess the effects of F11R/JAM-A blockade on platelet aggregation and thrombus formation using total thrombus formation analysis system. Effects of F11R/JAM-A blockade on thrombus formation in vivo were evaluated in murine models of carotid artery injury.
Results
F11R/JAM-A was not capable of capturing flowing blood platelets alone but enhanced platelet adhesion to fibrinogen under flow conditions. Blocking of F11R/JAM-A homophilic interactions with specific monoclonal antibodies or with recombinant F11R/JAM-A impaired thrombus formation in vitro in human blood and in vivo in the models of thrombosis in mice.
Conclusion
Interactions of F11R/JAM-A located on flowing platelets with its surface-bound counterpart enhance platelet binding to fibrinogen under high shear stress conditions. Blocking of these homophilic interactions compromises thrombus formation. While previously published studies pointed at a significant role of soluble F11R/JAM-A in priming platelets during thrombus formation, our results highlight the role of surface-bound F11R/JAM-A in this process.
Publication History
Received: 19 September 2024
Accepted: 11 March 2025
Accepted Manuscript online:
25 March 2025
Article published online:
18 April 2025
© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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