The ability of platelet extracellular vesicles to promote adhesion of monocytes cells to endothelium (360G-Wellcome-207131_Z_17_Z)

There is an increasing realisation that haemostatic and inflammatory responses to tissue damage are linked by common mediators. Adhesive and signaling interactions between platelets and leukocytes have been well-described. Recently it has been realised that some of these interactions are actually mediated through extracellular vesicles (PEV) released by the platelets. Indeed, we find that PEV can bind to leukocytes and to endothelial cells, transducing signals and transferring adhesion receptors, and thus potentially amplifying inflammatory leukocyte recruitment. Here we aim to further expand our investigations by evaluating the specific ability of PEV once bound to endothelial cells, to support adhesion of monocytes. Building on our own previous observations where PEV were able to bind to endothelial cells and support adhesion of neutrophils, we will test the concentration and time dependence of PEV binding to the endothelial cells and how this modifies monocyte and lymphocyte adhesion. Based on their high avidity for PEV in suspension, we hypothesise that monocytes are particularly sensitive to interactions with PEV deposited on endothelial cells. This study will test whether this is correct, and supply further evidence as to whether PEV are potent players in the thrombo-inflammatory response, for example, linked with pathogenesis of atherosclerosis.