Cargando…

Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition

Several studies have suggested that there is a link between membrane attack complex (MAC) deposition in the retina and the progression of diabetic retinopathy (DR). Our recent investigation demonstrated that circulating IgG-laden extracellular vesicles contribute to an increase in retinal vascular p...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Chao, Fisher, Kiera P., Hammer, Sandra S., Busik, Julia V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084203/
https://www.ncbi.nlm.nih.gov/pubmed/32121610
http://dx.doi.org/10.3390/ijms21051693
_version_ 1783508667606237184
author Huang, Chao
Fisher, Kiera P.
Hammer, Sandra S.
Busik, Julia V.
author_facet Huang, Chao
Fisher, Kiera P.
Hammer, Sandra S.
Busik, Julia V.
author_sort Huang, Chao
collection PubMed
description Several studies have suggested that there is a link between membrane attack complex (MAC) deposition in the retina and the progression of diabetic retinopathy (DR). Our recent investigation demonstrated that circulating IgG-laden extracellular vesicles contribute to an increase in retinal vascular permeability in DR through activation of the complement system. However, the mechanism through which extracellular vesicle-induced complement activation contributes to retinal vascular cytolytic damage in DR is not well understood. In this study, we demonstrate that IgG-laden extracellular vesicles in rat plasma activate the classical complement pathway, and in vitro Streptozotocin (STZ)-induced rat diabetic plasma results in MAC deposition and cytolytic damage in human retinal endothelial cells (HRECs). Moreover, removal of the plasma extracellular vesicles reduced the MAC deposition and abrogated cytolytic damage seen in HRECs. Together, the results of this study demonstrate that complement activation by IgG-laden extracellular vesicles in plasma could lead to MAC deposition and contribute to endothelium damage and progression of DR.
format Online
Article
Text
id pubmed-7084203
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70842032020-03-24 Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition Huang, Chao Fisher, Kiera P. Hammer, Sandra S. Busik, Julia V. Int J Mol Sci Article Several studies have suggested that there is a link between membrane attack complex (MAC) deposition in the retina and the progression of diabetic retinopathy (DR). Our recent investigation demonstrated that circulating IgG-laden extracellular vesicles contribute to an increase in retinal vascular permeability in DR through activation of the complement system. However, the mechanism through which extracellular vesicle-induced complement activation contributes to retinal vascular cytolytic damage in DR is not well understood. In this study, we demonstrate that IgG-laden extracellular vesicles in rat plasma activate the classical complement pathway, and in vitro Streptozotocin (STZ)-induced rat diabetic plasma results in MAC deposition and cytolytic damage in human retinal endothelial cells (HRECs). Moreover, removal of the plasma extracellular vesicles reduced the MAC deposition and abrogated cytolytic damage seen in HRECs. Together, the results of this study demonstrate that complement activation by IgG-laden extracellular vesicles in plasma could lead to MAC deposition and contribute to endothelium damage and progression of DR. MDPI 2020-03-01 /pmc/articles/PMC7084203/ /pubmed/32121610 http://dx.doi.org/10.3390/ijms21051693 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Chao
Fisher, Kiera P.
Hammer, Sandra S.
Busik, Julia V.
Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
title Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
title_full Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
title_fullStr Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
title_full_unstemmed Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
title_short Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
title_sort extracellular vesicle-induced classical complement activation leads to retinal endothelial cell damage via mac deposition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084203/
https://www.ncbi.nlm.nih.gov/pubmed/32121610
http://dx.doi.org/10.3390/ijms21051693
work_keys_str_mv AT huangchao extracellularvesicleinducedclassicalcomplementactivationleadstoretinalendothelialcelldamageviamacdeposition
AT fisherkierap extracellularvesicleinducedclassicalcomplementactivationleadstoretinalendothelialcelldamageviamacdeposition
AT hammersandras extracellularvesicleinducedclassicalcomplementactivationleadstoretinalendothelialcelldamageviamacdeposition
AT busikjuliav extracellularvesicleinducedclassicalcomplementactivationleadstoretinalendothelialcelldamageviamacdeposition