ABSTRACT
Background: CD34+ progenitor cells play an important role in haematopoiesis and vascular homeostasis. The aim of the present study was to investigate the role of platelet-derived junctional adhesion molecule-C (JAM-C) in adhesion and differentiation of human CD34+ cells in vitro, as well as its association with platelet-derived P-selectin in patients with coronary artery disease. 
Methods and Results: Using flow cytometry we observed that JAM-C expression on the surface of platelets is increased after activation with thrombin receptor activating peptide-6 in vitro and correlated with platelet-derived P-selectin expression in patients with coronary artery disease (r=0.301, P=0.01). The role of JAM-C and its counter receptor MAC-1 in adhesion of human CD34+ cells over immobilized platelets was investigated by using a neutralizing soluble protein (sJAM-C-Fc) and a monoclonal antibody against JAM-C or integrin MAC-1 (CD11b/CD18). Treatment with soluble JAM-C-Fc or anti-JAM-C or anti-MAC-1, but not with control-Fc or IgG1, resulted in a significantly decreased adhesion of human CD34+ cells to platelets under static conditions (P<0.05). In order to validate our findings under high shear stress we performed flow chamber experiments. In a similar manner, inhibiting JAM-C interaction with MAC-1 resulted in a significantly decreased adhesion of CD34+ cells over immobilized platelets under high shear stress (P<0.05). Colony forming unit assays and coculture assays revealed that inhibition of JAM-C/MAC-1 axis did not influence the platelet-mediated differentiation of CD34+ cells to endothelial cells or to macrophages/foam cells. 
Conclusions: Taken together a platelet-derived JAM-C supports CD34+ cell adhesion, a mechanism potentially involved in homing as well as domiciliation of human CD34+ cells.