Transendothelial migration drives dissociation of plateletmonocyte complexes.

Monocytes and platelets are both crucially involved in atherogenesis. Importantly, activated platelets bound to circulating monocytes increase adhesion of the monocytes and thus mediate colocalization of both cell types at the vessel wall. We examined the fate of the platelets upon migration of these potentially pro-atherogenic platelet-monocyte complexes (PMC) across activated endothelium. Platelet-monocyte complex migration was studied both quantitatively by means of Transwell filters coated with endothelial cells, as well as qualitatively with different imaging techniques, and in the absence or presence of flow. Upon PMC transendothelial migration, platelets relocate with monocytic P-selectin glycoprotein ligand-1 (PSGL-1) to the rear of the monocyte, detach, and remain at the endothelial surface. Platelet dissociation appeared not to be due to reduced PSGL-1 expression or reduced platelet-binding capacity of the migrated monocytes. In addition, different endothelial matrix proteins with different platelet-binding capacities coated on the Transwell filter, instead of endothelial cells, did not affect PMC dissociation. In contrast, lowering the mechanical stress that PMC experience during transmigration prevented dissociation of platelets. In conclusion, PMC dissociate during transendothelial migration as a result of monocytic PSGL-1 redistribution and mechanical stress. PMC-mediated deposition of activated platelets at sites of vascular inflammation is likely relevant for cardiovascular disease progression or vascular regeneration.