期刊
JOURNAL OF IMMUNOLOGY
卷 195, 期 7, 页码 3382-3389出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1500937
关键词
-
类别
资金
- Biotechnology and Biological Sciences Research Council
- Wellcome Trust [093445]
- Fight for Sight Ph.D. studentship award
- Biotechnology and Biological Sciences Research Council [BB/I019707/1] Funding Source: researchfish
- Fight for Sight [1833/84] Funding Source: researchfish
- Medical Research Council [MR/M02282X/1] Funding Source: researchfish
- BBSRC [BB/I019707/1] Funding Source: UKRI
- MRC [MR/M02282X/1] Funding Source: UKRI
Retinal pigment epithelial (RPE) cell death is a hallmark of age-related macular degeneration. The alternative pathway of complement activation is strongly implicated in RPE cell dysfunction and loss in age-related macular degeneration; therefore, it is critical that RPE cells use molecular strategies to mitigate the potentially harmful effects of complement attack. We show that the terminal complement complex C5b-9 assembles rapidly on the basal surface of cultured primary porcine RPE cells but disappears over 48 h without any discernable adverse effects on the cells. However, in the presence of the dynamin inhibitor dynasore, C5b-9 was almost completely retained at the cell surface, suggesting that, under normal circumstances, it is eliminated via the endocytic pathway. In support of this idea, we observed that C5b-9 colocalizes with the early endosome marker EEA1 and that, in the presence of protease inhibitors, it can be detected in lysosomes. Preventing the endocytosis of C5b-9 by RPE cells led to structural defects in mitochondrial morphology consistent with cell stress. We conclude that RPE cells use the endocytic pathway to prevent the accumulation of C5b-9 on the cell surface and that processing and destruction of C5b-9 by this route are essential for RPE cell survival.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据