Cargando…
CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis
INTRODUCTION: CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. MET...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325944/ https://www.ncbi.nlm.nih.gov/pubmed/25596646 http://dx.doi.org/10.1186/s13075-015-0518-4 |
_version_ | 1782356871808548864 |
---|---|
author | Karpus, Olga N Kiener, Hans P Niederreiter, Birgit Yilmaz-Elis, A Seda van der Kaa, Jos Ramaglia, Valeria Arens, Ramon Smolen, Josef S Botto, Marina Tak, Paul P Verbeek, J Sjef Hamann, Jörg |
author_facet | Karpus, Olga N Kiener, Hans P Niederreiter, Birgit Yilmaz-Elis, A Seda van der Kaa, Jos Ramaglia, Valeria Arens, Ramon Smolen, Josef S Botto, Marina Tak, Paul P Verbeek, J Sjef Hamann, Jörg |
author_sort | Karpus, Olga N |
collection | PubMed |
description | INTRODUCTION: CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. METHODS: Synovial tissue, primary FLS cultures, and three-dimensional FLS micromasses were analyzed. CD55 expression was assessed by quantitative polymerase chain reaction (PCR), in situ hybridization, flow cytometry, and immunohistochemistry. Reticular fibers were visualized by Gomori staining and colocalization of CD55 with extracellular matrix (ECM) proteins by confocal microscopy. Membrane-bound CD55 was released from synovial tissue with phospholipase C. Functional consequences of CD55 expression were studied in the K/BxN serum transfer model of arthritis using mice that in addition to CD55 also lack FcγRIIB (CD32), increasing susceptibility for immune complex-mediated pathology. RESULTS: Abundant CD55 expression seen in FLS of the intimal lining layer was associated with linearly oriented reticular fibers and was resistant to phospholipase C treatment. Expression of CD55 colocalized with collagen type I and III as well as with complement C3. A comparable distribution of CD55 was established in three-dimensional micromasses after ≥3 weeks of culture together with the ECM. CD55 deficiency did not enhance K/BxN serum-induced arthritis, but further exaggerated disease activity in Fcgr2b(−/−) mice. CONCLUSIONS: CD55 is produced by FLS and deposited on the local collagen fiber meshwork, where it protects the synovial tissue against immune complex-mediated arthritis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0518-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4325944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43259442015-02-13 CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis Karpus, Olga N Kiener, Hans P Niederreiter, Birgit Yilmaz-Elis, A Seda van der Kaa, Jos Ramaglia, Valeria Arens, Ramon Smolen, Josef S Botto, Marina Tak, Paul P Verbeek, J Sjef Hamann, Jörg Arthritis Res Ther Research Article INTRODUCTION: CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. METHODS: Synovial tissue, primary FLS cultures, and three-dimensional FLS micromasses were analyzed. CD55 expression was assessed by quantitative polymerase chain reaction (PCR), in situ hybridization, flow cytometry, and immunohistochemistry. Reticular fibers were visualized by Gomori staining and colocalization of CD55 with extracellular matrix (ECM) proteins by confocal microscopy. Membrane-bound CD55 was released from synovial tissue with phospholipase C. Functional consequences of CD55 expression were studied in the K/BxN serum transfer model of arthritis using mice that in addition to CD55 also lack FcγRIIB (CD32), increasing susceptibility for immune complex-mediated pathology. RESULTS: Abundant CD55 expression seen in FLS of the intimal lining layer was associated with linearly oriented reticular fibers and was resistant to phospholipase C treatment. Expression of CD55 colocalized with collagen type I and III as well as with complement C3. A comparable distribution of CD55 was established in three-dimensional micromasses after ≥3 weeks of culture together with the ECM. CD55 deficiency did not enhance K/BxN serum-induced arthritis, but further exaggerated disease activity in Fcgr2b(−/−) mice. CONCLUSIONS: CD55 is produced by FLS and deposited on the local collagen fiber meshwork, where it protects the synovial tissue against immune complex-mediated arthritis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13075-015-0518-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-17 2015 /pmc/articles/PMC4325944/ /pubmed/25596646 http://dx.doi.org/10.1186/s13075-015-0518-4 Text en © Karpus et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Karpus, Olga N Kiener, Hans P Niederreiter, Birgit Yilmaz-Elis, A Seda van der Kaa, Jos Ramaglia, Valeria Arens, Ramon Smolen, Josef S Botto, Marina Tak, Paul P Verbeek, J Sjef Hamann, Jörg CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
title | CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
title_full | CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
title_fullStr | CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
title_full_unstemmed | CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
title_short | CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
title_sort | cd55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4325944/ https://www.ncbi.nlm.nih.gov/pubmed/25596646 http://dx.doi.org/10.1186/s13075-015-0518-4 |
work_keys_str_mv | AT karpusolgan cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT kienerhansp cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT niederreiterbirgit cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT yilmazelisaseda cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT vanderkaajos cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT ramagliavaleria cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT arensramon cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT smolenjosefs cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT bottomarina cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT takpaulp cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT verbeekjsjef cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis AT hamannjorg cd55depositedonsynovialcollagenfibersprotectsfromimmunecomplexmediatedarthritis |