title: Human CD14 mediates recognition and phagocytosis of apoptotic cells.
abstract: Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by phagocytes without inducing inflammation. Here we show that the glycosylphosphatidylinositol-linked plasma-membrane glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells. CD14 can also act as a receptor that binds bacterial lipopolysaccharide (LPS), triggering inflammatory responses. Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome. Here we show that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells. This interaction depends on a region of CD14 that is identical to, or at least closely associated with, a region known to bind LPS. However, apoptotic cells, unlike LPS, do not provoke the release of pro-inflammatory cytokines from macrophages. These results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with 'non-self' components (LPS) and 'self' components (apoptotic cells) produce distinct macrophage responses.
authors.affiliation: Department of Immunology, University of Birmingham Medical School, UK.
authors.forename: A
authors.initials: A
authors.lastname: Devitt
authors.forename: O D
authors.initials: OD
authors.lastname: Moffatt
authors.forename: C
authors.initials: C
authors.lastname: Raykundalia
authors.forename: J D
authors.initials: JD
authors.lastname: Capra
authors.forename: D L
authors.initials: DL
authors.lastname: Simmons
authors.forename: C D
authors.initials: CD
authors.lastname: Gregory
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D019556:COS Cells; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D017634:Self Tolerance; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha