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.
Highlights
Properdin was originally described in 1954 by Pillemer et al as a serum component that promotes complement activation in an antibody-independent manner (Pillemer et al, 1954)
C3b and properdin deposition on A. fumigatus incubated in normal human serum was C3-dependent
Normal human serum (NHS) was used as a complement source and C3b deposition and properdin binding were determined on A. fumigatus with or without the addition of Cp40
Summary
Properdin was originally described in 1954 by Pillemer et al as a serum component that promotes complement activation in an antibody-independent manner (Pillemer et al, 1954). Controversies on how properdin facilitates complement activation have encircled. The first of the two common conceptions are well accepted. Properdin binds to and stabilizes the alternative C3 convertase C3bBb, thereby extending its half-life 5- to 10-fold and inhibit its degradation by factor I (Fearon and Austen, 1975; Schreiber et al, 1975; Medicus et al, 1976). Since challenged in 1958 by Nelson et al, who suggested that the binding of properdin requires the presence
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