2008年5月
Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus
JOURNAL OF LEUKOCYTE BIOLOGY
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- 巻
- 83
- 号
- 5
- 開始ページ
- 1300
- 終了ページ
- 1307
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1189/jlb.1107730
- 出版者・発行元
- FEDERATION AMER SOC EXP BIOL
Mouse milk fat globule epidermal growth factor 8 (MFG-E8), which is secreted by a subset of activated macrophages, binds to apoptotic cells by recognizing phosphatidylserine and promotes their engulfment. Many apoptotic cells are left unengulfed in the germinal centers of the spleen in MFG-E8(-/-) mice, and these mice develop an autoimmune disease resembling human systemic lupus erythematosus (hSLE). Here, we report that hMFG-E8 bound to phosphatidylserine and an integrin alpha(v)beta(3) complex. Increasing concentrations of MFG-E8 generated a bell-shaped response curve for the efficiency of phagocytosis. That is, in NIH3T3 and MFG-E8(-/-) thioglycollate-elicited peritoneal macrophages that do not express MFG-E8, hMFG-E8 enhanced engulfment at low concentrations but inhibited it at high concentrations. On the other hand, hMFG-E8 dose-dependently inhibited the engulfment of apoptotic cells by MFG-E8(-/-) thioglycollate-elicited peritoneal macrophages, indicating that an excess of MFG-E8 has an inverse effect on the engulfment of apoptotic cells. To investigate the role of MFG-E8 in human disease, we generated two mAb against MFG-E8 and screened human blood samples for MFG-E8 using an ELISA. We found that some childhood-onset and adult SLE patients carried a significant level of MFG-E8 in their blood samples. These results suggested that the aberrant expression of MFG-E8 is involved in the pathoetiology of some cases of hSLE.
- リンク情報
- ID情報
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- DOI : 10.1189/jlb.1107730
- ISSN : 0741-5400
- PubMed ID : 18303131
- Web of Science ID : WOS:000258019500026