title: Macrophage activation switching: an asset for the resolution of inflammation.
abstract: Macrophages play a central role in inflammation and host defence against microorganisms, but they also participate actively in the resolution of inflammation after alternative activation. However, it is not known whether the resolution of inflammation requires alternative activation of new resting monocytes/macrophages or if proinflammatory activated macrophages have the capacity to switch their activation towards anti-inflammation. In order to answer this question, we first characterized differential human macrophage activation phenotypes. We found that CD163 and CD206 exhibited mutually exclusive induction patterns after stimulation by a panel of anti-inflammatory molecules, whereas CCL18 showed a third, overlapping, pattern. Hence, alternative activation is not a single process, but provides a variety of different cell populations. The capacity of macrophages to switch from one activation state to another was then assessed by determining the reversibility of CD163 and CD206 expression and of CCL18 and CCL3 production. We found that every activation state was rapidly and fully reversible, suggesting that a given cell may participate sequentially in both the induction and the resolution of inflammation. These findings may provide new insight into the inflammatory process as well as new fields of investigation for immunotherapy in the fields of chronic inflammatory diseases and cancer.
authors.affiliation: Laboratoire de Neuro-Immuno-Virologie, Service de Neurovirologie UMR-E1, Université Paris-Sud, Centre de Recherches du Service de Santé des Armées, IPSC, Fontenay aux Roses, France.
authors.forename: F
authors.initials: F
authors.lastname: Porcheray
authors.forename: S
authors.initials: S
authors.lastname: Viaud
authors.forename: A-C
authors.initials: AC
authors.lastname: Rimaniol
authors.forename: C
authors.initials: C
authors.lastname: Léone
authors.forename: B
authors.initials: B
authors.lastname: Samah
authors.forename: N
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: D
authors.initials: D
authors.lastname: Dormont
authors.forename: G
authors.initials: G
authors.lastname: Gras
mesh_terms: D000893:Anti-Inflammatory Agents / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C111792:CCL18 protein, human; D000098902:CD163 Antigen; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D016207:Cytokines; D006684:HLA-DR Antigens; D037181:Lectins, C-Type; D019402:Macrophage Inflammatory Proteins; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface