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.
| Original language | English |
|---|---|
| Article number | e60908 |
| Journal | eLife |
| Volume | 9 |
| Pages (from-to) | 1-19 |
| Number of pages | 19 |
| ISSN | 2050-084X |
| DOIs | |
| Publication status | Published - Sept 2020 |
Keywords
- alternative pathway
- collectin-12
- immunology
- infectious disease
- inflammation
- microbiology
- properdin
- the complement system