title: Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages.
abstract: Macrophages are dynamic cells that mature under the influence of signals from the local microenvironment into either classically (M1) or alternatively (M2) activated macrophages with specific functional and phenotypic properties. Although the phenotypic identification of M1 and M2 macrophages is well established in mice, this is less clear for human macrophages. In addition, the persistence and reversibility of polarized human phenotypes is not well established. Human peripheral blood monocytes were differentiated into uncommitted macrophages (M0) and then polarized to M1 and M2 phenotypes using LPS/IFN-γ and IL-4/IL-13, respectively. M1 and M2 were identified as CD64(+)CD80(+) and CD11b(+)CD209(+), respectively, by flow cytometry. Polarized M1 cells secreted IP-10, IFN-γ, IL-8, TNF-α, IL-1β, and RANTES, whereas M2 cells secreted IL-13, CCL17, and CCL18. Functionally, M2 cells were highly endocytic. In cytokine-deficient medium, the polarized macrophages reverted back to the M0 state within 12 days. If previously polarized macrophages were given the alternative polarizing stimulus after 6 days of resting in cytokine-deficient medium, a switch in polarization was seen (i.e., M1 macrophages switched to M2 and expressed CD11b(+)CD209(+) and vice versa). In summary, we report phenotypic identification of human M1 and M2 macrophages, their functional characteristics, and their ability to be reprogrammed given the appropriate stimuli.
authors: 1 Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, The University of Queensland, Brisbane, Queensland, Australia; and.
authors: Abdullah A
authors: AA
authors: Tarique
authors: 1 Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, The University of Queensland, Brisbane, Queensland, Australia; and.
authors: Jayden
authors: J
authors: Logan
authors: 1 Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, The University of Queensland, Brisbane, Queensland, Australia; and.
authors: Emma
authors: E
authors: Thomas
authors: 1 Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, The University of Queensland, Brisbane, Queensland, Australia; and.|2 Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.
authors: Patrick G
authors: PG
authors: Holt
authors: 1 Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, The University of Queensland, Brisbane, Queensland, Australia; and.
authors: Peter D
authors: PD
authors: Sly
authors: 1 Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, The University of Queensland, Brisbane, Queensland, Australia; and.
authors: Emmanuelle
authors: E
authors: Fantino
mesh_terms: D002454:Cell Differentiation; D054414:Chemokine CCL17 / Q000096:biosynthesis / Q000378:metabolism; D018946:Chemokine CCL5 / Q000096:biosynthesis / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000378:metabolism; D019742:Chemokines, CC / Q000096:biosynthesis / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D061251:Primary Cell Culture; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
chemical_list: C106230:CCL17 protein, human; C111792:CCL18 protein, human; C114753:CXCL10 protein, human; D054414:Chemokine CCL17; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019742:Chemokines, CC; D018793:Interleukin-13; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: alternatively activated macrophages (AAM/M2); classically activated macrophages (CAM/M1); phagocytosis/endocytosis; phenotypic stability; reprogramming of polarization