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Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells
Proteinase 3 (PR3) is the autoantigen in granulomatosis with polyangiitis, an autoimmune necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Moreover, PR3 is a serine protease whose membrane expression can potentiate inflammatory diseases such as ANCA-associated va...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932363/ https://www.ncbi.nlm.nih.gov/pubmed/29755460 http://dx.doi.org/10.3389/fimmu.2018.00818 |
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author | Tacnet-Delorme, Pascale Gabillet, Julie Chatfield, Simon Thieblemont, Nathalie Frachet, Philippe Witko-Sarsat, Véronique |
author_facet | Tacnet-Delorme, Pascale Gabillet, Julie Chatfield, Simon Thieblemont, Nathalie Frachet, Philippe Witko-Sarsat, Véronique |
author_sort | Tacnet-Delorme, Pascale |
collection | PubMed |
description | Proteinase 3 (PR3) is the autoantigen in granulomatosis with polyangiitis, an autoimmune necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Moreover, PR3 is a serine protease whose membrane expression can potentiate inflammatory diseases such as ANCA-associated vasculitis and rheumatoid arthritis. During apoptosis, PR3 is co-externalized with phosphatidylserine (PS) and is known to modulate the clearance of apoptotic cells through a calreticulin (CRT)-dependent mechanism. The complement protein C1q is one mediator of efferocytosis, the clearance of altered self-cells, particularly apoptotic cells. Since PR3 and C1q are both involved in the clearance of apoptotic cells and immune response modulation and share certain common ligands (i.e., CRT and PS), we examined their possible interaction. We demonstrated that C1q binding was increased on apoptotic rat basophilic leukemia (RBL) cells that expressed PR3, and we demonstrated the direct interaction between purified C1q and PR3 molecules as shown by surface plasmon resonance. To better understand the functional consequence of this partnership, we tested C1q-dependent phagocytosis of the RBL cell line expressing PR3 and showed that PR3 impaired C1q enhancement of apoptotic cell uptake. These findings shed new light on the respective roles of C1q and PR3 in the elimination of apoptotic cells and suggest a novel potential axis to explore in autoimmune diseases characterized by a defect in apoptotic cell clearance and in the resolution of inflammation. |
format | Online Article Text |
id | pubmed-5932363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59323632018-05-11 Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells Tacnet-Delorme, Pascale Gabillet, Julie Chatfield, Simon Thieblemont, Nathalie Frachet, Philippe Witko-Sarsat, Véronique Front Immunol Immunology Proteinase 3 (PR3) is the autoantigen in granulomatosis with polyangiitis, an autoimmune necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Moreover, PR3 is a serine protease whose membrane expression can potentiate inflammatory diseases such as ANCA-associated vasculitis and rheumatoid arthritis. During apoptosis, PR3 is co-externalized with phosphatidylserine (PS) and is known to modulate the clearance of apoptotic cells through a calreticulin (CRT)-dependent mechanism. The complement protein C1q is one mediator of efferocytosis, the clearance of altered self-cells, particularly apoptotic cells. Since PR3 and C1q are both involved in the clearance of apoptotic cells and immune response modulation and share certain common ligands (i.e., CRT and PS), we examined their possible interaction. We demonstrated that C1q binding was increased on apoptotic rat basophilic leukemia (RBL) cells that expressed PR3, and we demonstrated the direct interaction between purified C1q and PR3 molecules as shown by surface plasmon resonance. To better understand the functional consequence of this partnership, we tested C1q-dependent phagocytosis of the RBL cell line expressing PR3 and showed that PR3 impaired C1q enhancement of apoptotic cell uptake. These findings shed new light on the respective roles of C1q and PR3 in the elimination of apoptotic cells and suggest a novel potential axis to explore in autoimmune diseases characterized by a defect in apoptotic cell clearance and in the resolution of inflammation. Frontiers Media S.A. 2018-04-25 /pmc/articles/PMC5932363/ /pubmed/29755460 http://dx.doi.org/10.3389/fimmu.2018.00818 Text en Copyright © 2018 Tacnet-Delorme, Gabillet, Chatfield, Thieblemont, Frachet and Witko-Sarsat. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Tacnet-Delorme, Pascale Gabillet, Julie Chatfield, Simon Thieblemont, Nathalie Frachet, Philippe Witko-Sarsat, Véronique Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells |
title | Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells |
title_full | Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells |
title_fullStr | Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells |
title_full_unstemmed | Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells |
title_short | Proteinase 3 Interferes With C1q-Mediated Clearance of Apoptotic Cells |
title_sort | proteinase 3 interferes with c1q-mediated clearance of apoptotic cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932363/ https://www.ncbi.nlm.nih.gov/pubmed/29755460 http://dx.doi.org/10.3389/fimmu.2018.00818 |
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