Autoimmune disease and impaired uptake of apoptotic cells in MFG-E8-deficient mice

被引：829

作者：

Hanayama, R

Tanaka, M

Miyasaka, K

Aozasa, K

Koike, M

Uchiyama, Y

Nagata, S

机构：

[1] Osaka Univ, Sch Med, Dept Genet, Osaka 5650871, Japan

[2] Osaka Univ, Sch Med, Dept Pathol, Osaka 5650871, Japan

[3] Osaka Univ, Sch Med, Dept Cell Biol & Neurosci, Osaka 5650871, Japan

[4] RIKEN, Res Ctr Allergy & Immunol, Lab Innate Cellular Immun, Kanagawa 2300045, Japan

[5] Osaka Univ, Grad Sch Frontier Biosci, Integrated Biol Labs, Genet Lab, Suita, Osaka 5650871, Japan

[6] Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Suita, Osaka 5650871, Japan

来源：

SCIENCE | 2004年 / 304卷 / 5674期

关键词：

D O I：

10.1126/science.1094359

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 [理学]; 0710 [生物学]; 09 [农学];

摘要：

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.

引用

页码：1147 / 1150

页数：4

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