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Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, wheth...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511233/ https://www.ncbi.nlm.nih.gov/pubmed/32909942 http://dx.doi.org/10.7554/eLife.60908 |
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author | Zhang, Jie Song, Lihong Pedersen, Dennis V Li, Anna Lambris, John D Andersen, Gregers Rom Mollnes, Tom Eirik Ma, Ying Jie Garred, Peter |
author_facet | Zhang, Jie Song, Lihong Pedersen, Dennis V Li, Anna Lambris, John D Andersen, Gregers Rom Mollnes, Tom Eirik Ma, Ying Jie Garred, Peter |
author_sort | Zhang, Jie |
collection | PubMed |
description | Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b-dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3-depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defense bridging pattern recognition and specific AP activation. |
format | Online Article Text |
id | pubmed-7511233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-75112332020-09-25 Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement Zhang, Jie Song, Lihong Pedersen, Dennis V Li, Anna Lambris, John D Andersen, Gregers Rom Mollnes, Tom Eirik Ma, Ying Jie Garred, Peter eLife Immunology and Inflammation Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern-recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b-dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3-depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defense bridging pattern recognition and specific AP activation. eLife Sciences Publications, Ltd 2020-09-10 /pmc/articles/PMC7511233/ /pubmed/32909942 http://dx.doi.org/10.7554/eLife.60908 Text en © 2020, Zhang et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Zhang, Jie Song, Lihong Pedersen, Dennis V Li, Anna Lambris, John D Andersen, Gregers Rom Mollnes, Tom Eirik Ma, Ying Jie Garred, Peter Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement |
title | Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement |
title_full | Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement |
title_fullStr | Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement |
title_full_unstemmed | Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement |
title_short | Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement |
title_sort | soluble collectin-12 mediates c3-independent docking of properdin that activates the alternative pathway of complement |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511233/ https://www.ncbi.nlm.nih.gov/pubmed/32909942 http://dx.doi.org/10.7554/eLife.60908 |
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