Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
- Rigshospitalet/Copenhagen University, Denmark
- Aarhus University, Denmark
- University of Pennsylvania, United States
- University of Oslo, Norway
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 defence bridging pattern recognition and specific AP activation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Gregers Rom Andersen
Funding
Kirsten og Freddy Johansens Fond (Research fund)
- Ying Jie Ma
Novo Nordisk (Research fund)
- Peter Garred
Købmand I Odense Johan og Hanne Weimann Født Seedorffs Legat (Research fund)
- Ying Jie Ma
Alfred Benzon Foundation (Research fund)
- Ying Jie Ma
- Peter Garred
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
eLife 9:e60908.
https://doi.org/10.7554/eLife.60908
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