Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
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Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement. / Zhang, Jie; Song, Lihong; Pedersen, Dennis V; Li, Anna; Lambris, John D; Andersen, Gregers Rom; Mollnes, Tom Eirik; Ma, Ying Jie; Garred, Peter.
In: eLife, Vol. 9, e60908, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement
AU - Zhang, Jie
AU - Song, Lihong
AU - Pedersen, Dennis V
AU - Li, Anna
AU - Lambris, John D
AU - Andersen, Gregers Rom
AU - Mollnes, Tom Eirik
AU - Ma, Ying Jie
AU - Garred, Peter
N1 - © 2020, Zhang et al.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Aspergillus fumigatus/immunology
KW - Collectins/blood
KW - Complement C3/metabolism
KW - Complement Pathway, Alternative/immunology
KW - HEK293 Cells
KW - Humans
KW - Properdin/analysis
KW - Protein Binding/immunology
U2 - 10.7554/eLife.60908
DO - 10.7554/eLife.60908
M3 - Journal article
C2 - 32909942
VL - 9
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e60908
ER -
ID: 269535633