Platelet Interaction with Bone Marrow Derived CD34⁺ Stem Cells: Potential Role of Chemoattractant Chemerin

Chemerin is a 16 kDa chemoattractant circulating in blood in an inactive form (prochemerin). Its chemotactic activity is released following proteolytic cleavage of its labile carboxyl-terminal amino acids by proteases of the coagulation, fibrinolytic and inflammatory cascades. Chemokine-like receptor 1 (CMKLR1) is a chemerin receptor expressed on plasmacytoid dendritic cells, natural killer cells and tissue macrophages. We identified the expression of CMKLR1 on mouse CD34 positive (CD34⁺) bone marrow-derived stem cells (BMSC) using anti-mouse CMKLR1 antibody by FACS. Fluorescein-labeled CD34⁺/CMKLR1⁺ BMSC adhered to immobilized chemerin dose-dependently. The EC50 of BMSC adhesion to human and mouse chemerin is 2.5 and 5 ug/mL respectively. BMSCs also adhered to SDF-1 (stromal cell-derived factor-1) with EC50 of 0.3 ug/mL, but did not bind to immobilized fibronectin. We have previously reported that platelets express chemerin and release it upon activation. CMKLR1 is also expressed on platelet surface as demonstrated by FACS. Immobilized chemerin could induce platelet adhesion and CD62P (p-selectin) expression as detected by fluorescein-labeled anti-CD62P antibody. BMSC formed complexes with both resting and activated platelets as demonstrated by fluorescein-labeled washed platelets incubated with unlabeled mouse CD34+/CMKLR1+ BMSCs using FACS analysis. Both anti-chemerin and anti-CD62P antibodies could partially block BMSCs binding to immobilized platelets at 50% and 35% respectively. In conclusion, chemerin directly mediates platelets interaction with BMSCs. Chemerin also facilitates platelet/BMSC complex formation by inducing platelet p-selectin (CD62P) expression. Platelet-derived chemerin, similar to SDF-1, may be involved in tissue regeneration by inducing progenitor cells mobilization and differentiation.