Complement Factor H-Related 3 Enhanced Inflammation and Complement Activation in Human RPE Cells
| Autor: | Diana Pauly, Sabine Amslinger, Herbert Jägle, Delia M Ormenisan, Nicole Schäfer, Volker Enzmann, Anas Rasras |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
oxidative stress epitopes
Epithelial-Mesenchymal Transition Inflammasomes Cell Immunology RPE cells FHR-3 alters RPE cell complosome Gene Expression Macrophage-1 Antigen Inflammation 610 Medicine & health Complement factor I Retinal Pigment Epithelium complosome AMD Polymorphism Single Nucleotide Cell Line Macular Degeneration NLR Family Pyrin Domain-Containing 3 Protein medicine Immunology and Allergy Humans Anaphylatoxin Receptor Complement Activation Original Research Chemistry FHR-3 RETC-2 Epithelial Cells Blood Proteins Complement C3 RC581-607 Complement system Cell biology medicine.anatomical_structure HEK293 Cells inflammation Factor H Complement Factor H embryonic structures 570 Life sciences biology Cytokine secretion Immunologic diseases. Allergy medicine.symptom |
| Zdroj: | Frontiers in Immunology Schäfer, Nicole; Rasras, Anas; Ormenisan, Delia M; Amslinger, Sabine; Enzmann, Volker; Jägle, Herbert; Pauly, Diana (2021). Complement Factor H-Related 3 Enhanced Inflammation and Complement Activation in Human RPE Cells. Frontiers in immunology, 12, p. 769242. Frontiers Research Foundation 10.3389/fimmu.2021.769242 Frontiers of Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.769242 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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