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    Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice (2004)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2004-05-25
    Description: Apoptotic cells expose phosphatidylserine and are swiftly engulfed by macrophages. Milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and that enhances the engulfment of apoptotic cells by macrophages. We report that tingible body macrophages in the germinal centers of the spleen and lymph nodes strongly express MFG-E8. Many apoptotic lymphocytes were found on the MFG-E8-/- tingible body macrophages, but they were not efficiently engulfed. The MFG-E8-/- mice developed splenomegaly, with the formation of numerous germinal centers, and suffered from glomerulonephritis as a result of autoantibody production. These data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in the germinal centers and that its failure can lead to autoimmune diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanayama, Rikinari -- Tanaka, Masato -- Miyasaka, Kay -- Aozasa, Katsuyuki -- Koike, Masato -- Uchiyama, Yasuo -- Nagata, Shigekazu -- New York, N.Y. -- Science. 2004 May 21;304(5674):1147-50.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15155946" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Antinuclear/blood ; Antigens, CD/analysis ; Antigens, Differentiation, Myelomonocytic/analysis ; *Antigens, Surface ; *Apoptosis ; Autoantibodies/biosynthesis/blood ; Autoimmune Diseases/*immunology ; B-Lymphocytes/immunology ; Blotting, Northern ; Female ; Gene Targeting ; Germinal Center/cytology/immunology/metabolism ; Glomerulonephritis/*immunology ; In Situ Nick-End Labeling ; Macrophage Activation ; Macrophages/immunology/*metabolism/ultrastructure ; Macrophages, Peritoneal/immunology/metabolism ; Membrane Glycoproteins/genetics/*metabolism ; Mice ; *Milk Proteins ; *Phagocytosis ; Phosphatidylserines/metabolism ; Protein Binding ; Spleen/cytology/metabolism/pathology ; Splenomegaly/pathology ; T-Lymphocytes/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-07-13
    Description: A classic feature of apoptotic cells is the cell-surface exposure of phosphatidylserine (PtdSer) as an "eat me" signal for engulfment. We show that the Xk-family protein Xkr8 mediates PtdSer exposure in response to apoptotic stimuli. Mouse Xkr8(-/-) cells or human cancer cells in which Xkr8 expression was repressed by hypermethylation failed to expose PtdSer during apoptosis and were inefficiently engulfed by phagocytes. Xkr8 was activated directly by caspases and required a caspase-3 cleavage site for its function. CED-8, the only Caenorhabditis elegans Xk-family homolog, also promoted apoptotic PtdSer exposure and cell-corpse engulfment. Thus, Xk-family proteins have evolutionarily conserved roles in promoting the phagocytosis of dying cells by altering the phospholipid distribution in the plasma membrane.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Suzuki, Jun -- Denning, Daniel P -- Imanishi, Eiichi -- Horvitz, H Robert -- Nagata, Shigekazu -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Jul 26;341(6144):403-6. doi: 10.1126/science.1236758. Epub 2013 Jul 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23845944" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/chemistry/genetics/*metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Calcium/metabolism ; Caspases/metabolism ; Cell Line ; Cell Line, Tumor ; Cell Membrane/*metabolism ; CpG Islands ; Humans ; Macrophages/physiology ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Knockout ; Molecular Sequence Data ; *Phagocytosis ; Phosphatidylserines/*metabolism ; Recombinant Fusion Proteins/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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