Homophilic interactions of platelet F11R/JAM-A with its surface-bound counterpart facilitate thrombus formation.

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 of platelets under static conditions, suppresses the activation of the platelet αIIbβ3 integrin and was shown to activate blood platelets as soluble form via homophilic interaction.

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 platelets 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.