Autor: |
Jie Zhang, Lihong Song, Dennis V Pedersen, Anna Li, John D Lambris, Gregers Rom Andersen, Tom Eirik Mollnes, Ying Jie Ma, Peter Garred |
Jazyk: |
angličtina |
Rok vydání: |
2020 |
Předmět: |
|
Zdroj: |
eLife, Vol 9 (2020) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.60908 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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