Immunophenotypic characterisation of human monocyte subsets: Possible implications for cardiovascular disease pathophysiology.

Background: 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 characterisation of human monocyte subsets. Patients/methods: Analysis of surface markers of blood and bone marrow monocyte subsets and functional characterisation of blood monocyte subsets in healthy volunteers was performed by flow cytometry. Results: In this 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 CD14lowCD16+CCR2-(Mon3) subsets. In comparison to the classical Mon1, the Mon2 subset had the highest expression of Tie2, CXCR4, CD163, CD115, receptors to ICAM-1, VEGF, and the highest surface levels of apolipoprotein B and ferritin. In contrast, the Mon3 had maximal expression of VCAM-1 receptors and CD204. Mon2 and Mon3 subsets had significantly lower activity of NFκB pathway than Mon1. Mon1 and Mon2 had similar phagocytic activity, which was significantly higher compared to 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 to 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 characterised Mon2 population may represent the previously reported pluripotent progenitor/pro-angiogenic monocytes.