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

Abstract

Objective: Far beyond hemostasis and thrombosis, significant evidence has indicated the critical role of platelets in atherosclerosis. SDF-1 is among the pro-inflammatory chemokines that are increased in platelets of patients with coronary artery disease (CAD). The goal of the current work is to identify the in vitro effect of platelets from either CAD patients or healthy volunteers on the induction of macrophages and foam cells. Materials and Methods: The expression of SDF-1 on platelet surfaces in CAD patients and healthy volunteers was investigated using flow cytometry. We also evaluated the CXCR4/CXCR7 expression on monocytes from buffy coats of healthy volunteers. The effect of platelets from CAD patients and healthy volunteers on differentiation of monocytes and foam cell formation was evaluated using Oil Red O (ORO) staining. Flow cytometry and real-time PCR were also employed to evaluate surface markers and mRNA expression of genes involved in 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 marker of M2 macrophage, and upregulate the mRNA expression of the SRB, CD36, ACAT, LXR-α, and ABCA1 genes in monocytes. Notably, platelets of CAD patients with higher expression of SDF-1, increased the expression of genes encoding SRB and CD36 as compared to platelets of healthy volunteers. Conclusion: Our results indicate that platelets from CAD patients could provoke monocyte differentiation into macrophages with an M2 phenotype, which in turn may participate in an atheroprotective process.

Keywords

• sdf-1
• monocytes
• platelets
• co-culture
• foam cells