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
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