| RRC ID |
67482
|
| 著者 |
Yamaguchi H, Takagi J, Miyamae T, Yokota S, Fujimoto T, Nakamura S, Ohshima S, Naka T, Nagata S.
|
| タイトル |
Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus.
|
| ジャーナル |
J Leukoc Biol
|
| Abstract |
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.
|
| 巻・号 |
83(5)
|
| ページ |
1300-7
|
| 公開日 |
2008-5-1
|
| DOI |
10.1189/jlb.1107730
|
| PII |
jlb.1107730
|
| PMID |
18303131
|
| MeSH |
3T3 Cells
Adult
Animals
Antigens, Surface / blood*
Antigens, Surface / genetics*
Biomarkers / blood
Child
Humans
Lupus Erythematosus, Systemic / blood*
Macrophages / physiology*
Mice
Mice, Knockout
Milk Proteins / blood*
Milk Proteins / genetics*
Phagocytosis
Phospholipids / blood
Recombinant Proteins / metabolism
U937 Cells
|
| IF |
3.757
|
| リソース情報 |
| 遺伝子材料 |
pEF-human MFG-E8/Flag (RDB18995) |
