Immunophenotypic characterization of human monocyte subsets: possible implications for cardiovascular disease pathophysiology

Objectives: Monocytes include several subsets with different and sometimes divergent roles in immunity, atherogenesis and reparative processes. Objectives: We aimed to perform detailed immunophenotypic and functional characterization of human monocyte subsets. Patients/methods: Analysis of surface markers of blood and bone marrow monocyte subsets and functional characterization of blood monocyte subsets in healthy volunteers was performed using flow cytometry. Results: In the present study, we show the presence of three subsets which could be unequivocally distinguished by surface expression of CD14, CD16 and CCR2 as CD14(+)CD16(-)CCR2(+) (Mon1), CD14(+)CD16(+) CCR2(+)(Mon2) and CD14(low)CD16(+)CCR2(-)(Mon3) subsets. In comparison with the classic Mon1, the Mon2 subset had the highest expression of Tie2, CXCR4, CD163, CD115, receptors to inter-cellular adhesion molecule-1 (ICAM-1), vascular endothelial growth factor (VEGF), and the highest surface levels of apolipoprotein B and ferritin. In contrast, Mon3 had maximal expression of VCAM-1 receptors and CD204. The Mon2 and Mon3 subsets had significantly lower activity of the NF kappa B pathway than Mon1. Mon1 and Mon2 had similar phagocytic activity, which was significantly higher compared with Mon3. All three subsets were present in bone marrow, although the relative proportion of Mon2 in bone marrow was about 2.5-fold higher compared with that seen in blood. Significant differences in cytokine production in response to endotoxin stimulation were observed between the three monocyte subsets. Conclusion: Given their immunophenotypic similarity, the newly characterized Mon2 population may represent the previously reported pluripotent progenitor/pro-angiogenic monocytes.