Platelet Aggregates-Induced Human CD34+Progenitor Cell Proliferation and Differentiation to Macrophages and Foam Cells Is Mediated by Stromal Cell Derived Factor 1 in Vitro

Abstract

The chemokine stromal cell derived factor 1 (SDF-1) regulates chemotactic recruitment (homing) and differentiation of CD34 (+) stem cells. Platelets express substantial amounts of SDF-1 upon activation. The aim of the present study was to evaluate the role of SDF-1 in platelet-induced proliferation and differentiation of human CD34 (+) cells to macrophages and foam cells, as well as in regulation of matrix metalloproteinase (MMP)-9 secretion. Co-culture experiments of platelet thrombi (2 x 10(8)/mL) with human CD34 (+) progenitor cells resulted in platelet phagocytosis by the latter, causing their differentiation into CD68-positive macrophages and subsequent Sudan red III-positive foam cells. Platelet aggregates-induced foam cell generation and MMP-9 secretion were attenuated by a neutralizing monoclonal antibody against platelet-derived SDF-1, as evaluated by immunofluorescence microscopy and gelatin zymography. Co-culture experiments of human arterial endothelial cells and human CD34 (+) progenitor cells resulted in a fourfold increased proliferation of CD34 (+) cells in the presence of platelets being mainly regulated by platelet-derived SDF-1 in vitro. These findings imply that in the presence of platelet thrombi, CD34 (+) progenitor cells phagocytize platelets in an SDF-1 dependent manner, causing their differentiation into macrophages and then foam cells, a mechanism most likely contributing to atherogenesis and atheroprogression.