Complement component C5a activates ICAM-1 expression on human choroidal endothelial cells
Open accessAbstract
PURPOSE: The complement system plays a crucial role in the progression of age-related macular degeneration (AMD). In this study, the authors sought to evaluate the pathophysiologic roles of complement components C3a and C5a in the human choroid in AMD. METHODS: Human RPE/choroid was assayed for the presence of C3a and C5a receptors (C3aR and C5aR) using RT-PCR and immunohistochemistry. Choroidal endothelial cell migration and proliferation were evaluated in the presence of C5a. Organ cultures of human choroid were incubated in C5a or bovine serum albumin (BSA) followed by quantitative immunohistochemistry and quantitative PCR for ICAM-1. AMD patients and controls were genotyped at SNPs in the C5R1 and C3AR1 genes. RESULTS: C5aR, but not C3aR, was detected in human choroid. C5a did not promote endothelial cell migration or proliferation. However, choriocapillaris endothelial cells in organ culture responded to C5a by increasing ICAM-1 mRNA and protein. No significant association of SNP genotypes was detected in AMD patients at the C3AR1 and C5R1 genes. CONCLUSIONS: The generation of C5a peptides may lead to activation of choriocapillaris endothelial cells in AMD. Activation of the choroidal endothelium may affect the progression of AMD by recruitment of monocytes, leading to additional sequelae of AMD pathogenesis.
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In the choriocapillaris, C5a upregulates the expression of leukocyte adhesion molecules on endothelial cells and plays a key role in recruiting γδ T-cells.
“Furthermore, in the choriocapillaris, C5a upregulates the expression of leukocyte adhesion molecules on endothelial cells [109] and plays a key role in recruiting γδ T-cells [194]”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [109]
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References 63 · Cited by 114
Research works printed but not linked: 2
- Walport MJ. Complement: first of two parts. N Engl J Med. 2001; 344:1058 -1066.
- Walport MJ. Complement: second of two parts. N Engl J Med. 2001;344:1140 -1144.
- Authors
- Skeie, J. M., Fingert, J. H., Russell, S. R., Stone, E. M., & Mullins, R. F.
- Affiliations
- University of Iowa (US)
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2010-10-01
- Volume
- 51
- Issue
- 10
- Pages
- 5336
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC3066598
- OpenAlex
- W2073924928
- Cited by
- 114
- References
- 63
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 13 · 2014: 11 · 2013: 3 · 2012: 7
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness
- Macula Vision Research Foundation
- Directorate for Biological Sciences
- National Eye Institute (R01EY017451, F32EY022280, EY016822, R01EY016822, EY017451)
- National Institute of Child Health and Human Development
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- C5a, ICAM-1, choroidal endothelial cells, choriocapillaris, age-related macular degeneration, complement C3a, C5a receptor, C3a receptor, endothelial cell migration, endothelial cell proliferation, C3AR1, single nucleotide polymorphisms, monocyte recruitment
- MeSH terms
- Cell Movement, Choroid, Endothelium, Vascular, Gene Expression Regulation, Genotype, Humans, Immunohistochemistry, Macular Degeneration, Organ Culture Techniques, Receptors, Complement, RNA, Messenger, Complement C3a, Complement C5a, Intercellular Adhesion Molecule-1, Reverse Transcriptase Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Receptor, Anaphylatoxin C5a
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