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dc.contributor.authorZhang, Jie
dc.contributor.authorSong, Lihong
dc.contributor.authorPedersen, Dennis V.
dc.contributor.authorLi, Anna
dc.contributor.authorLambris, John D.
dc.contributor.authorAndersen, Gregers Rom
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorMa, Ying Jie
dc.contributor.authorGarred, Peter
dc.date.accessioned2021-06-02T06:35:18Z
dc.date.available2021-06-02T06:35:18Z
dc.date.issued2020-09-10
dc.description.abstractProperdin 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.citationZhang, 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:e60908:1-19en_US
dc.identifier.cristinIDFRIDAID 1883672
dc.identifier.doi10.7554/ELIFE.60908
dc.identifier.issn2050-084X
dc.identifier.urihttps://hdl.handle.net/10037/21316
dc.language.isoengen_US
dc.publishereLife Sciences Publicationsen_US
dc.relation.journaleLIFE
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleSoluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complementen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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