Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice.
Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice.
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DOI：
10.1084/jem.20040342
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发表时间：
2004-08-16
期刊：
影响因子：
--
通讯作者：
Tanaka M
中科院分区：
文献类型：
--
作者：
Asano K;Miwa M;Miwa K;Hanayama R;Nagase H;Nagata S;Tanaka M
凋亡细胞被专职吞噬细胞如巨噬细胞和树突细胞迅速吞噬。该过程防止潜在有害或免疫原性细胞内物质从死亡细胞中释放，并且被认为对维持周围组织的正常功能起关键作用。由活化的巨噬细胞和未成熟树突状细胞分泌的乳脂球EGF因子8（MFG-E8）连接凋亡细胞和吞噬细胞，并促进凋亡细胞的吞噬作用。在这里，我们报告的MFG-E8突变体，指定为D89 E，携带点突变的RGD基序，抑制不仅由各种各样的吞噬细胞的凋亡细胞的吞噬作用，但也抑制了巯基乙酸盐引起的腹腔巨噬细胞吞噬凋亡细胞的IL-10的产生增强。当静脉注射到小鼠体内时，D89 E蛋白诱导产生自身抗体，包括抗磷脂抗体和抗核抗体。通过共注射同系凋亡胸腺细胞，自身抗体的产生得到增强。在D89 E诱导自身抗体产生后，治疗的小鼠显示出自身抗体滴度的长期升高，并在肾小球中形成IgG沉积。这些结果表明，凋亡细胞吞噬功能的损害导致自身抗体的产生。
Apoptotic cells are rapidly phagocytosed by professional phagocytes, such as macrophages and dendritic cells. This process prevents the release of potentially noxious or immunogenic intracellular materials from dying cells, and is thought to play a critical role for the maintenance of normal functions in surrounding tissues. Milk fat globule-EGF-factor 8 (MFG-E8), secreted by activated macrophages and immature dendritic cells, links apoptotic cells and phagocytes, and promotes phagocytosis of apoptotic cells. Here, we report that an MFG-E8 mutant, designated as D89E, carrying a point mutation in an RGD motif, inhibited not only the phagocytosis of apoptotic cells by a wide variety of phagocytes, but also inhibited the enhanced production of IL-10 by thioglycollate-elicited peritoneal macrophages phagocytosing apoptotic cells. When intravenously injected into mice, the D89E protein induced the production of autoantibodies including antiphospholipids antibodies and antinuclear antibodies. The production of autoantibodies was enhanced by the coinjection of syngeneic apoptotic thymocytes. After the induction of autoantibody production by D89E, the treated mice showed a long-term elevation of the titer for autoantibodies, and developed IgG deposition in the glomeruli. These results indicated that the impairment of apoptotic cell phagocytosis led to autoantibody production.
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影响因子：
82.9
作者：
Millar, DG;Garza, KM;Ohashi, PS
通讯作者：
Ohashi, PS
影响因子：
15.9
作者：
GHARAVI, AE;SAMMARITANO, LR;ELKON, KB
通讯作者：
ELKON, KB
影响因子：
4.4
作者：
Byrne, A;Reen, DJ
通讯作者：
Reen, DJ
DOI：
10.1073/pnas.95.16.9535
发表时间：
1998-08-04
影响因子：
11.1
作者：
Oka, K;Sawamura, T;Masaki, T
通讯作者：
Masaki, T
影响因子：
64.8
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM