title: Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells.
abstract: The aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor beta1, but lower concentrations of tumour necrosis factor alpha, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine.
authors.affiliation: Department of Medicine and Therapeutics, University of Aberdeen, UK. r.n.barker@abdn.ac.uk
authors.forename: R N
authors.initials: RN
authors.lastname: Barker
authors.forename: L-P
authors.initials: LP
authors.lastname: Erwig
authors.forename: K S K
authors.initials: KS
authors.lastname: Hill
authors.forename: A
authors.initials: A
authors.lastname: Devine
authors.forename: W P
authors.initials: WP
authors.lastname: Pearce
authors.forename: A J
authors.initials: AJ
authors.lastname: Rees
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000276:immunology / Q000502:physiology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009504:Neutrophils; D010587:Phagocytosis; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: D019013:CD40 Antigens; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma