Expression of milk fat globule epidermal growth factor 8 in immature dendritic cells for engulfment of apoptotic cells
Expression of milk fat globule epidermal growth factor 8 in immature dendritic cells for engulfment of apoptotic cells
复制标题
DOI：
10.1002/eji.200424930
复制
发表时间：
2004-05-01
影响因子：
5.4
通讯作者：
Nagata, S
中科院分区：
文献类型：
--
作者：
Miyasaka, K;Hanayama, R;Nagata, S
乳脂球表皮生长因子8 （MFG-E8）是一种刺激凋亡细胞被吞噬细胞吞噬的蛋白质。在这里，我们发现，在粒细胞-巨噬细胞集落刺激因子（GM-CSF）存在的情况下，通过体外培养骨髓祖细胞产生的小鼠未成熟树突状细胞（DC）和皮肤中的朗格汉斯细胞表达MFG-E8。M-CSF产生的骨髓源性巨噬细胞不表达MFG-E8。在未成熟DC中表达的MFG-E8被发现以外泌体的形式分泌。脂多糖诱导未成熟DC成熟后，MFG-E8的表达明显受到抑制。MFG-E8的表达与细胞吞噬凋亡细胞的能力密切相关。也就是说，未成熟的DC比成熟的DC或骨髓源性巨噬细胞更有效地吞噬凋亡细胞。mfg - e8缺失小鼠制备的未成熟DC吞噬凋亡细胞的能力严重降低。这些结果表明MFG-E8在骨髓源性未成熟DC吞噬凋亡细胞中起重要作用。
Milk fat globule epidermal growth factor 8 (MFG-E8) is a protein that stimulates the engulfment of apoptotic cells by phagocytes. Here, we show that mouse immature dendritic cells (DC) generated in vitro by culturing bone marrow progenitors in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), and Langerhans cells present in the skins, expressed MFG-E8. Bone marrow-derived macrophages generated by M-CSF did not express MFG-E8. MFG-E8 expressed in immature DC was found to be secreted as exosomes. The expression of MFG-E8 was significantly suppressed when the immature DC were induced to mature by treating them with lipopolysaccharides. This expression of MFG-E8 was well correlated with the ability of the cells to engulf apoptotic cells. That is, immature DC phagocytosed apoptotic cells more efficiently than did mature DC or bone marrow-derived macrophages. The ability of immature DC to engulf apoptotic cells was severely reduced when the immature DC were prepared from MFG-E8-deficient mice. These results indicated that MFG-E8 plays an essential role in the engulfment of apoptotic cells by bone marrow-derived immature DC.