Figure 2.

Mechanisms of platelet-mediated leukocyte recruitment: (1) appropriately activated endothelial cells express a matrix of VWF on their surface to which platelets are recruited and activated. Platelet presented P-selectin then forms an adhesive bridge between the endothelial surface and blood borne leukocytes. (2) Platelets form heterotypic aggregates with leukocytes in the circulation in a P-selectin dependent manner. Aggregates are then recruited to the VWF on the surface of appropriately activated endothelial cells. (3) Inflammatory cytokines induce transcriptional programmes in endothelial cells which result in the expression of adhesion molecules and chemokines that support leukocyte adhesion. Leukocytes in heterotypic aggregates which are recruited to the endothelial cell surface posses additional platelet borne receptors. These can in turn support the secondary adhesion of un-aggregated leukocytes. (4) Upon activation platelets shed microvesicles which bind directly to endothelial cells. Microvesicle borne inflammatory cytokines induce transcriptional programmes in endothelial cells which result in the expression of adhesion molecules and chemokines that support leukocyte adhesion. (5) P-selectin bearing PMV bind to appropriately activated endothelial cells. Platelet presented P-selectin then forms an adhesive bridge between the endothelial surface and blood borne leukocytes. (6) P-selectin bearing PMV form heterotypic aggregates with leukocytes in the circulation. Aggregates are then recruited to VWF on appropriately stimulated endothelial cells utilising microvesicle borne adhesion receptors.