Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages

Abstract

Objectives: Macrophages (Mφs) have various functions and play a critical role in host defense and the maintenance of homeostasis. Mφs exist in every tissue in the body, but Mφs from different tissues exhibit a wide range of phenotypes with regard to their morphology, cell surface antigen expression and function, and are called by different names. However, the precise mechanism of the generation of macrophage heterogeneity is not known. In the present study, the authors examined the functional heterogeneity of Mφs generated from human monocytes under the influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF). Methodology: CD14 positive human monocytes (Mos) were incubated with M-CSF and GM-CSF for 6-7 days to stimulate the generation of M-CSF-induced monocyte-derived Mφs (M-Mφs) and GM-CSF-induced monocyte-derived Mφs (GM-Mφs), respectively. The expression of cell surface antigens and several functions such as antigen presenting cell activity, susceptibility to oxidant stress, and the susceptibility to HIV-1 and mycobacterium tuberculosis infection were examined. Results: GM-Mφs and M-Mφs are distinct in their morphology, cell surface antigen expression, and functions examined. The phenotype of GM-Mφs closely resembles that of human Alveolar-Mφs (A-Mφs), indicating that CSF-induced human monocyte-derived Mφs are useful to clarify the molecular mechanism of heterogeneity of human Mφs, and GM-Mφs will become a model of human A-Mφs.