ArticleFrontiers in immunology2021
Complement Factor H-Related 3 Enhanced Inflammation and Complement Activation in Human RPE Cells.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Decoding the Factor H-Related Proteins: Gatekeepers of Complement Dysregulation in AMD.European journal of immunology · 2026Review
- Exploring Biomarkers and Mechanisms of Action of Adaptive Immune Response in Age-Related Macular Degeneration Based on Transcriptomics.Biomedicines · 2026Article
- Systemic inflammation triggers local complement production in the mouse retina and RPE.Journal of neuroinflammation · 2026Article
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- The complement cascade in Alzheimer's disease: modern implications of an ancient immune protagonist.Molecular neurodegeneration · 2025Review
- Complement proteins associated with circulatory and glomerular IgA-containing immune complexes in patients with IgA nephropathy.Scientific reports · 2025Article
- The complement system in intestinal inflammation and cancer.The Journal of clinical investigation · 2025Review
- Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration.Journal of neuroinflammation · 2025Article
- Complement C3 Activation in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025Article
- The secret life of complement: challenges and opportunities in exploring functions of the complosome in disease.The Journal of clinical investigation · 2025Review
- Plasma Exosomal-Derived SERPINA1 and GNAI2 Downregulation as Potential Diagnostic Biomarkers of Kawasaki Disease with Coronary Artery Aneurysms.International journal of molecular sciences · 2025Article
- Non-canonical roles of CFH in retinal pigment epithelial cells revealed by dysfunctional rare CFH variants.Stem cell reports · 2025Article
- Dual role of complement in neuronal repair.Frontiers in immunology · 2025Review
- Canonical and non-canonical roles of complement in atherosclerosis.Nature reviews. Cardiology · 2024Review
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Hematopoiesis Revolves Around the Primordial Evolutional Rhythm of Purinergic Signaling and Innate Immunity - A Journey to the Developmental Roots.Stem cell reviews and reports · 2024Review
- The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.Journal of neuroinflammation · 2024Review
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- Complement, complosome, and complotype: A perspective.European journal of immunology · 2023Review
- Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma.International journal of molecular sciences · 2023Review
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement Factor H-Related 3 (FHR-3) is a major regulator of the complement system, which is associated with different diseases, such as age-related macular degeneration (AMD). However, the non-canonical local, cellular functions of FHR-3 remained poorly understood. Here, we report that FHR-3 bound to oxidative stress epitopes and competed with FH for interaction. Furthermore, FHR-3 was internalized by viable RPE cells and modulated time-dependently complement component (C3, FB) and receptor (C3aR, CR3) expression of human RPE cells. Independently of any external blood-derived proteins, complement activation products were detected. Anaphylatoxin C3a was visualized in treated cells and showed a translocation from the cytoplasm to the cell membrane after FHR-3 exposure. Subsequently, FHR-3 induced a RPE cell dependent pro-inflammatory microenvironment. Inflammasome NLRP3 activation and pro-inflammatory cytokine secretion of IL-1ß, IL-18, IL-6 and TNF-α were induced after FHR-3-RPE interaction. Our previously published monoclonal anti-FHR-3 antibody, which was chimerized to reduce immunogenicity, RETC-2-ximab, ameliorated the effect of FHR-3 on ARPE-19 cells. Our studies suggest FHR-3 as an exogenous trigger molecule for the RPE cell "complosome" and as a putative target for a therapeutic approach for associated degenerative diseases.
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