Abstract
We have recently shown that oxidative stress of ARPE-19 cells alters the expression of the cell surface complement regulatory proteins DAF and CD59, and permits increased activation of complement when the cells are subsequently exposed to serum. Based upon these results, we hypothesized that RPE cells respond to cellular stress as if it is infection, and reduce their surface expression of complement regulatory proteins to foster the local immune response. To test this hypothesis, we examined whether cellular hypoxia would produce a similar change in ARPE-19 cells. In addition, we asked whether this response to oxidative stress is universal in all epithelial cells, by examining the expression of complement regulatory proteins on the surface of the renal and pulmonary epithelial cells. We found that the expression of complement regulatory proteins is altered by aseptic cellular stressors such as hypoxia and oxidative stress, but the response to these conditions differs from tissue to tissue. In RPE cells oxidative stress reduces the expression of the cell surface complement regulators and sensitizes the cells to complement mediated injury. This specific response is not seen in epithelial cells from the lung or kidney, and is not induced by hypoxia. These studies help explain the unique mechanisms by which uncontrolled complement activation may contribute to the development of AMD.
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Acknowledgments
This work was supported in part by National Institutes of Health Grants DK077661 and DK076690 (JMT), DK035081 (MKP), EY13520 and EY017465 (BR) and HL082485 (ST), a vision core grant (EY014793), the Foundation Fighting Blindness, American Heart Association grant 0735101Â N (VPF), a grant from the Sandler Program for Asthma Research (VMH), and an unrestricted grant to MUSC from Research to Prevent Blindness, Inc., New York, NY. BR is a Research to Prevent Blindness Olga Keith Weiss Scholar. The authors thank Luanna Bartholomew for editorial assistance. The authors declare the following disclosures. VMH is a co-founder of Taligen Therapeutics, Inc., which develops complement inhibitors for therapeutic use; JMT, VMH and BR are consultants for Taligen Therapeutics, Inc.
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Thurman, J.M., Renner, B., Kunchithapautham, K., Holers, V.M., Rohrer, B. (2010). Aseptic Injury to Epithelial Cells Alters Cell Surface Complement Regulation in a Tissue Specific Fashion. In: Anderson, R., Hollyfield, J., LaVail, M. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 664. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1399-9_18
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DOI: https://doi.org/10.1007/978-1-4419-1399-9_18
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