Accumulation of immune complexes in glomerular disease is independent of locally synthesized c3
Open accessAbstract
Although complement activation can make immune complex glomerulonephritis worse, the third complement component also can solubilize immune complexes and thus reduce the severity of disease. How C3 that is produced within the kidney contributes to this balance is unknown. This study therefore investigated the relative roles of systemic and local C3 production in a model of glomerular immune complex disease. Injection of sheep anti-glomerular basement membrane antibody into preimmunized mice resulted in accumulation of immune complexes and progressive loss of function over 14 d that was much more marked in C3-deficient (C3-/-) mice. In C3-sufficient mice that received a transplant of a C3-/- mouse kidney and in C3-/- mice with C3-sufficient mouse kidney transplants, the severity and the pattern of injury went with the complement status of the recipient. That is, mice with deficient circulating C3 developed severe glomerular immune complex disease, whereas those with a high level of circulating C3 had well-preserved glomerular structure and function. It is concluded that circulating C3 is a critical factor in reducing the glomerular accumulation of immune complexes. Local synthesis of C3 did not have a major influence on this aspect of glomerular disease.
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In experimental mouse models, the fenestrated capillaries of the renal glomerulus are more prone to systemic C3 activation.
“while the fenestrated capillaries of the renal glomerulus are more prone to systemic C3 activation [204,207].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [207]
In experimental mouse models, the renal tubular epithelium is more susceptible to donor kidney-derived C3.
“in experimental mouse models, the renal tubular epithelium has been found to be more susceptible to donor kidney-derived C3”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [207]
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- Authors
- Sheerin, N. S., Abe, K., Risley, P., & Sacks, S. H.
- Affiliations
- Guy's Hospital (GB)
- Corresponding author
- Sheerin, Neil S.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2006-03
- Volume
- 17
- Issue
- 3
- Pages
- 686-696
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2100487993
- Cited by
- 22
- References
- 46
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 1 · 2012: 1
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
- Keywords
- immune complex glomerulonephritis, complement C3, anti-glomerular basement membrane antibody, kidney transplantation, C3-deficient mice, complement activation, glomerular injury
- MeSH terms
- Analysis of Variance, Animals, Antibodies, Autoantibodies, Biopsy, Needle, Complement C3, Disease Models, Animal, Female, Glomerulonephritis, Immune Complex Diseases, Immunohistochemistry, Injections, Subcutaneous, Kidney Function Tests, Mice, Inbred C57BL, Probability, Sensitivity and Specificity, Mice
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