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Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement.

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 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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7511233 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement.

Zhang Jie J Song Lihong L Pedersen Dennis V DV Li Anna A Lambris John D JD Andersen Gregers Rom GR Mollnes Tom Eirik TE Ma Ying Jie YJ Garred Peter P

eLife 20200910

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 m ...[more]

PMID: 32909942

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Dataset Information

Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement.

Publications

Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement.

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