Retinal Pigment Epithelial Cells Mitigate the Effects of Complement Attack by Endocytosis of C5b-9

The Journal of Immunology : Official Journal of the American Association of Immunologists
Apostolos GeorgiannakisStephen E Moss

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-...Continue Reading

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Citations

Jul 20, 2016·Proceedings of the National Academy of Sciences of the United States of America·Li Xuan TanAparna Lakkaraju
Jul 20, 2018·Investigative Ophthalmology & Visual Science·David A CoplandAndrew D Dick
Mar 4, 2020·International Journal of Molecular Sciences·Chao HuangJulia V Busik
Aug 29, 2020·Journal of Cell Science·Tina StormClare E Futter
Mar 30, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tamara L LenisRoxana A Radu
Feb 23, 2020·Cell Reports·Kelly MulfaulSarah L Doyle
Dec 30, 2020·International Journal of Molecular Sciences·Emilie Grarup JensenThomas J Corydon
Feb 1, 2021·Experimental Eye Research·Ping YangGlenn J Jaffe
Feb 28, 2020·Progress in Retinal and Eye Research·Aparna LakkarajuDavid S Williams
Dec 16, 2020·Progress in Retinal and Eye Research·Benjamin J KimJohn D Lambris

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Methods Mentioned

BETA
electron microscopy
Cytomation
confocal microscopy
GTPase

Software Mentioned

ImageJ
Imaris

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