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

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  • Jie Zhang, Københavns Universitet, China Pharmaceutical University
  • ,
  • Lihong Song, Københavns Universitet, Shenyang Pharmaceutical University
  • ,
  • Dennis V. Pedersen
  • Anna Li, Københavns Universitet, China Pharmaceutical University
  • ,
  • John D. Lambris, University of Pennsylvania
  • ,
  • Gregers Rom Andersen
  • Tom Eirik Mollnes, University of Oslo, Norwegian University of Science and Technology
  • ,
  • Ying Jie Ma, Københavns Universitet
  • ,
  • Peter Garred, Københavns Universitet

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.

StatusUdgivet - sep. 2020

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