title: Reversible differentiation of pro- and anti-inflammatory macrophages.
abstract: Macrophages (Mφ) represent dynamic cell populations that develop according to the nature of environmental signals. It has been demonstrated that human Mφ can be polarized in vitro into pro-inflammatory (Mφ1) and anti-inflammatory cells (Mφ2) by the lineage-determining factors GM-CSF and M-CSF, respectively. Here we show that polarized Mφ1 and Mφ2 are not an end stage of differentiation but are able to reversibly undergo functional re-differentiation into anti-inflammatory and pro-inflammatory Mφ. GM-CSF-driven Mφ1 exposed to M-CSF for an additional 6 days obtained a Mφ2-like phenotype, inhibited the production of pro-inflammatory cytokine IL-6 and TNF-α, and exhibited a reduced T cell stimulatory capacity. Vice versa, Mφ2 exposed to GM-CSF exhibited a Mφ1-like phenotype with significant lower production of anti-inflammatory cytokine IL-10 and a higher T cell stimulatory activity, and a decreased capacity for phagocytosis of early apoptotic cells. Our data suggest that polarized macrophages are flexible in modulating their immune functions upon environmental changes, i.e., steady-state versus inflammatory conditions. These observations are important for our understanding of the regulatory role of macrophages in tissue homeostasis and disease pathogenesis.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhao
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor