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Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
- Source :
- International Journal of Molecular Sciences, International Journal of Molecular Sciences, Vol 21, Iss 5, p 1693 (2020), Volume 21, Issue 5
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
Abstract
- 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.
- Subjects :
- membrane attack complex (MAC)
Male
Cell Survival
Immunoglobulins
Vascular permeability
Complement Membrane Attack Complex
Article
Retina
Catalysis
Diabetes Mellitus, Experimental
lcsh:Chemistry
Rats, Sprague-Dawley
Inorganic Chemistry
Extracellular Vesicles
03 medical and health sciences
Classical complement pathway
chemistry.chemical_compound
0302 clinical medicine
human retinal endothelial cells (HRECs)
Complement C1
Extracellular
Animals
Humans
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Complement Activation
Molecular Biology
complement system
Spectroscopy
030304 developmental biology
0303 health sciences
retinal vascular damage
Cell Death
Organic Chemistry
Endothelial Cells
Retinal
General Medicine
Extracellular vesicle
3. Good health
Computer Science Applications
Complement system
Cell biology
Endothelial stem cell
diabetic retinopathy
lcsh:Biology (General)
lcsh:QD1-999
chemistry
Complement membrane attack complex
030215 immunology
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....54c1f91fbed35c4716bcc727675a8b46