title: MFG-E8-dependent clearance of apoptotic cells, and autoimmunity caused by its failure.
abstract: Apoptotic cells are swiftly engulfed by macrophages and immature dendritic cells. Inefficient clearance of apoptotic cells has been implicated as a cause of inflammation and autoimmune diseases. Milk fat globule-EGF factor 8 (MFG-E8) and developmental endothelial locus-1 (Del-1) are glycoproteins secreted from macrophages that pass apoptotic cells to phagocytes. MFG-E8, but not Del-1, is expressed in the tingible-body macrophages at the germinal centers of the second lymphoid tissues. MFG-E8-deficient mice carry many unengulfed apoptotic cells in the germinal centers of the spleen, and develop a lupus-like autoimmune disease. In this review, we discuss the importance of the MFG-E8-mediated clearance of apoptotic cells in the prevention of autoimmune diseases.
authors.affiliation: Department of Genetics, Osaka University Medical School, Osaka, Japan.
authors.forename: Rikinari
authors.initials: R
authors.lastname: Hanayama
authors.forename: Kay
authors.initials: K
authors.lastname: Miyasaka
authors.forename: Michio
authors.initials: M
authors.lastname: Nakaya
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Nagata
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000502:physiology*; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000209:etiology*; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology; D015815:Cell Adhesion Molecules; D003851:Deoxyribonucleases / Q000502:physiology; D018858:Germinal Center / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000502:physiology; D008894:Milk Proteins; D010587:Phagocytosis
chemical_list: D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; C098942:MFGE8 protein, human; D008894:Milk Proteins; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease