Figure 1. Heterogeneity of monocyte/macrophage and neutrophil.

Monocyte and neutrophil are originated from the same progenitor cell (GMP) that is differentiated from hematopoietic stem cell (HSC). GMP is able to differentiate into monocyte or myelocyte. When enter into tissues, monocytes become macrophages. Macrophages acquire distinct features when activated through different ways. “Classically” activated macrophages (M1) express CD11c, HLA-DR, and iNOS, secret TNF-α and MCP-1, while “alternatively” activated macrophages (M2) express CD206, CD163, CD209, IL-1r, arginase 1 and IL-10. In obesity/diabetes, polarization of macrophages skews towards to “M1”, which contributes to the maintenance of chronic inflammation and insulin resistance in various tissues. Similar to macrophages, neutrophils differentiated from myelocytes display different phenotype when activated in different environment. “N1” possesses a pro-inflammatory or anti-tumor phenotype, whereas “N2” driven by TGF-β displays anti-inflammatory or pro-tumor phenotype. Increased levels of CD95, TNF and ROS are responsible for the anti-tumor phenotype of “N1”, while higher levels of MMP-9 and arginase might contribute to the pro-tumor phenotype of “N2”. However, as the classification of “N1” and “N2” was not proposed until recently, it requires further studies to identify the “N1”- or “N2”-specific protein expression profile and their functional role in obesity/diabetes. Abbreviations: HSC: hematopoietic stem cell; GMP: Granulocyte-monocyte Progenitor; MPP: multiple potent progenitor; TNF: tumour necrosis factor; ROS: Reactive oxygen species; MMP-9: Matrix metallopeptidase 9; HLD-DR: human leukocyte antigens; iNOS: inducible nitric oxide synthase; MCP-1: monocyte chemoattractant protein-1; IL-1r: interleukin-1 receptor; IL-10: interleukin-10.