Soluble CD59 Expressed from an Adenovirus In Vivo Is a Potent Inhibitor of Complement Deposition on Murine Liver Vascular Endothelium
Open accessAbstract
Inappropriate activation of complement on the vascular endothelium of specific organs, or systemically, underlies the etiology of a number of diseases. These disorders include atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, atherosclerosis, age-related macular degeneration, diabetic retinopathy, and transplant rejection. Inhibition of the terminal step of complement activation, i.e. formation of the membrane attack complex, using CD59 has the advantage of retaining the upstream processes of the complement cascade necessary for fighting pathogens and retaining complement's crucial role in tissue homeostasis. Previous studies have shown the necessity of membrane targeting of soluble CD59 in order for it to prove an effective inhibitor of complement deposition both in vitro and in vivo. In this study we have generated an in vivo model of human complement activation on murine liver vascular endothelium. This model should prove useful for the development of anti-complement therapies for complement-induced pathologies of vascular endothelium. Using this model, we have demonstrated the viability of a non membrane-targeted soluble CD59 to significantly inhibit complement deposition on the endothelium of murine liver vasculature when expressed in vivo from an adenovirus. This result, unanticipated based on prior studies, suggests that the use of non membrane-targeted sCD59 as an anti-complement therapy be re-visited.
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Several experiments using mouse models of laser-induced CNV have demonstrated that all complement pathways, particularly the alternative and terminal pathways, play a significant role in angiogenesis.
“Several experiments using mouse models of laser-induced CNV have demonstrated that all complement pathways, particularly the alternative and terminal pathways, play a significant role in angiogenesis [150,152,153,154,155,156,157,158,159,160,161,162,163].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [158]
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Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44 · see citing works
- Authors
- Gandhi, J., Cashman, S. M., & Kumar-Singh, R.
- Affiliations
- Tufts University (US)
- ORCID
- Gandhi, Jarel
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-06-24
- Volume
- 6
- Issue
- 6
- Pages
- e21621
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3123367
- OpenAlex
- W2046478240
- Cited by
- 16
- References
- 40
- Citations by year
- 2026: 1 · 2023: 2 · 2019: 1 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 5
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Research to Prevent Blindness
- Ögonfonden
- National Institutes of Health
- National Eye Institute (EY014991, R01EY014991, EY 013887)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- complement deposition, membrane attack complex, terminal complement activation, anti-complement therapy, adenoviral gene expression, membrane targeting, mouse model
- MeSH terms
- Adenoviridae, Animals, Antibodies, Aorta, Blood Vessels, Complement Activation, Endothelium, Vascular, Humans, Injections, Intraperitoneal, Liver, Mice, Inbred C57BL, Organ Specificity, Protein Binding, Solubility, Complement Membrane Attack Complex, CD59 Antigens, Platelet Endothelial Cell Adhesion Molecule-1, Endothelial Cells, Serum, Mice
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