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

eLife

Lihong Song¹  Tom Eirik Mollnes¹  Anna Li²  John D Lambris³  Peter Garred³  Ying Jie Ma⁴  Jie Zhang⁵  Dennis V Pedersen⁵  Gregers Rom Andersen⁵ 

[1] Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China;Department of Pharmaceutical Science, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China;Department of Molecular Biology and Genetics, Center for Structural Biology, Aarhus University, Aarhus, Denmark;Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States;The Laboratory of Molecular Medicine, Department of Clinical Immunology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;

关键词: collectin-12;    properdin;    alternative pathway;    the complement system;   

DOI  :  10.7554/eLife.60908

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown