dc.contributor.author | Zhang, Jie | |
dc.contributor.author | Song, Lihong | |
dc.contributor.author | Pedersen, Dennis V. | |
dc.contributor.author | Li, Anna | |
dc.contributor.author | Lambris, John D. | |
dc.contributor.author | Andersen, Gregers Rom | |
dc.contributor.author | Mollnes, Tom Eirik | |
dc.contributor.author | Ma, Ying Jie | |
dc.contributor.author | Garred, Peter | |
dc.date.accessioned | 2021-06-02T06:35:18Z | |
dc.date.available | 2021-06-02T06:35:18Z | |
dc.date.issued | 2020-09-10 | |
dc.description.abstract | 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 <i>Aspergillus fumigatus</i> 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. | en_US |
dc.identifier.citation | Zhang, Song, Pedersen, Li, Lambris, Andersen, Mollnes, Ma, Garred. Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement. eLIFE. 2020;9:e60908:1-19 | en_US |
dc.identifier.cristinID | FRIDAID 1883672 | |
dc.identifier.doi | 10.7554/ELIFE.60908 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://hdl.handle.net/10037/21316 | |
dc.language.iso | eng | en_US |
dc.publisher | eLife Sciences Publications | en_US |
dc.relation.journal | eLIFE | |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2020 The Author(s) | en_US |
dc.subject | VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710 | en_US |
dc.subject | VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710 | en_US |
dc.title | Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |