Co-culture of Platelets with Monocytes Induced M2 Macrophage Polarization and Formation of Foam Cells: Shedding Light on the Crucial Role of Platelets in Monocyte Differentiation

摘要

Objective: Far beyond hemostasis and thrombosis, significantevidence has indicated the critical role of platelets in atherosclerosis.SDF-1 is among the pro-inflammatory chemokines that are increasedin platelets of patients with coronary artery disease (CAD). The goalof the current work is to identify the in vitro effect of plateletsfrom either CAD patients or healthy volunteers on the induction ofmacrophages and foam cells.Materials and Methods: The expression of SDF-1 on platelet surfacesin CAD patients and healthy volunteers was investigated usingflow cytometry. We also evaluated the CXCR4/CXCR7 expression onmonocytes from buffy coats of healthy volunteers. The effect ofplatelets from CAD patients and healthy volunteers on differentiationof monocytes and foam cell formation was evaluated using Oil Red O(ORO) staining. Flow cytometry and real-time PCR were also employedto evaluate surface markers and mRNA expression of genes involvedin this process after co-culture of platelets with monocytes.Results: Monocytes in co-culture with platelets acquired a spindleshape appearance and ORO-positive lipid droplets. In addition,platelets could induce CD163 expression, as an important markerof M2 macrophage, and upregulate the mRNA expression of theSRB, CD36, ACAT, LXR-α, and ABCA1 genes in monocytes. Notably,platelets of CAD patients with higher expression of SDF-1, increasedthe expression of genes encoding SRB and CD36 as compared toplatelets of healthy volunteers.Conclusion: Our results indicate that platelets from CAD patientscould provoke monocyte differentiation into macrophages with anM2 phenotype, which in turn may participate in an atheroprotectiveprocess.