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Retinal pigment epithelial cells mitigate the effects of complement attack by endocytosis of C5b-9

Georgiannakis, A; Burgoyne, T; Lueck, K; Futter, C; Greenwood, J; Moss, SE; (2015) Retinal pigment epithelial cells mitigate the effects of complement attack by endocytosis of C5b-9. Journal of Immunology , 195 (7) pp. 3382-3389. 10.4049/jimmunol.1500937. Green open access

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Abstract

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.

Type: Article
Title: Retinal pigment epithelial cells mitigate the effects of complement attack by endocytosis of C5b-9
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.4049/jimmunol.1500937
Publisher version: http://dx.doi/10.4049/jimmunol.1500937
Additional information: Copyright © 2015 The Authors. This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1473139
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