title: Subsets of human type 2 macrophages show differential capacity to produce reactive oxygen species.
abstract: Reactive oxygen species (ROS) produced by macrophages have recently been shown to have immunosuppressive properties and induce regulatory T cells. Here we investigated the ROS producing capacity of well-defined human Mph2 subsets and studied the contribution of ROS in the Mph-T cell interaction. Mph were generated from monocytes using M-CSF (Mph2), IL-4 (Mph2a), or IL-10 (Mph2c). Upon PMA stimulation, Mph2 and Mph2c showed a high ROS producing capacity, whereas this was low for Mph2a. Mph2 and Mph2c displayed a reduced T cell stimulatory capacity compared to Mph2a. Addition of the ROS inhibitor DPI decreased the T cell proliferation and IFN-γ production. When testing directly on Mph, DPI dose-dependently decreased the IL-10 and IL-12p40 production of CD40L-stimulated Mph2 subsets. In conclusion, the ROS producing capacity is different among human Mph type-2 subsets. In all cases, DPI suppressed T cell proliferation and cytokine production, indicating a ROS-dependent mechanism of T cell activation.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marina D
authors.initials: MD
authors.lastname: Kraaij
authors.forename: Karin M
authors.initials: KM
authors.lastname: Koekkoek
authors.forename: Sandra W
authors.initials: SW
authors.lastname: van der Kooij
authors.forename: Kyra A
authors.initials: KA
authors.lastname: Gelderman
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
mesh_terms: D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D009861:Onium Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C007517:diphenyleneiodonium; D016173:Macrophage Colony-Stimulating Factor
keywords: Cat; Catalase; DPI; Macrophage; Mph; NADPH oxidase; NOX2; ROS; T cell; catalase; diphenyleneiodonium; macrophage