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...
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| Format: | Article |
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eLife Sciences Publications Ltd
2020-09-01
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| Online Access: | https://elifesciences.org/articles/60908 |
| _version_ | 1811180314991525888 |
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| author | Jie Zhang Lihong Song Dennis V Pedersen Anna Li John D Lambris Gregers Rom Andersen Tom Eirik Mollnes Ying Jie Ma Peter Garred |
| author_facet | Jie Zhang Lihong Song Dennis V Pedersen Anna Li John D Lambris Gregers Rom Andersen Tom Eirik Mollnes Ying Jie Ma Peter Garred |
| author_sort | Jie Zhang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T09:00:49Z |
| format | Article |
| id | doaj.art-bfba14197f804b95a621fa5dcfd1c4d3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:00:49Z |
| publishDate | 2020-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bfba14197f804b95a621fa5dcfd1c4d32022-12-22T04:32:48ZengeLife Sciences Publications LtdeLife2050-084X2020-09-01910.7554/eLife.60908Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complementJie Zhang0https://orcid.org/0000-0002-4472-3468Lihong Song1Dennis V Pedersen2Anna Li3John D Lambris4Gregers Rom Andersen5https://orcid.org/0000-0001-6292-3319Tom Eirik Mollnes6Ying Jie Ma7https://orcid.org/0000-0003-4003-2579Peter Garred8The Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaThe Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, ChinaDepartment of Molecular Biology and Genetics, Center for Structural Biology, Aarhus University, Aarhus, DenmarkThe Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Molecular Biology and Genetics, Center for Structural Biology, Aarhus University, Aarhus, DenmarkDepartment of Immunology, Oslo University Hospital, and University of Oslo, Oslo, Norway; Research Laboratory, Nordland Hospital, K. G. Jebsen TREC, University of Tromsø, Bodø, Norway; Center of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, NorwayThe Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkThe Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkProperdin 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.https://elifesciences.org/articles/60908collectin-12properdinalternative pathwaythe complement system |
| spellingShingle | Jie Zhang Lihong Song Dennis V Pedersen Anna Li John D Lambris Gregers Rom Andersen Tom Eirik Mollnes Ying Jie Ma Peter Garred Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement eLife collectin-12 properdin alternative pathway the complement system |
| 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 | collectin-12 properdin alternative pathway the complement system |
| url | https://elifesciences.org/articles/60908 |
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