Document Detail


Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice.
MedLine Citation:
PMID:  15155946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Rikinari Hanayama; Masato Tanaka; Kay Miyasaka; Katsuyuki Aozasa; Masato Koike; Yasuo Uchiyama; Shigekazu Nagata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  304     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-24     Completed Date:  2004-06-14     Revised Date:  2007-03-19    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1147-50     Citation Subset:  IM    
Affiliation:
Department of Genetics, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/Antigens, CD; 0/Antigens, Differentiation, Myelomonocytic; 0/Antigens, Surface; 0/Autoantibodies; 0/CD68 antigen, human; 0/Membrane Glycoproteins; 0/Mfge8 protein, mouse; 0/Milk Proteins; 0/Phosphatidylserines
Comments/Corrections
Comment In:
Science. 2004 May 21;304(5674):1123-4   [PMID:  15155940 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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