An Evaluation of the Role of Properdin in Alternative Pathway Activation on Neisseria meningitidis and Neisseria gonorrhoeae

Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
The Journal of Immunology (Impact Factor: 4.92). 07/2010; 185(1):507-16. DOI: 10.4049/jimmunol.0903598
Source: PubMed


Properdin, a positive regulator of the alternative pathway (AP) of complement is important in innate immune defenses against invasive neisserial infections. Recently, commercially available unfractionated properdin was shown to bind to certain biological surfaces, including Neisseria gonorrhoeae, which facilitated C3 deposition. Unfractionated properdin contains aggregates or high-order oligomers, in addition to its physiological "native" (dimeric, trimeric, and tetrameric) forms. We examined the role of properdin in AP activation on diverse strains of Neisseria meningitidis and N. gonorrhoeae specifically using native versus unfractionated properdin. C3 deposition on Neisseria decreased markedly when properdin function was blocked using an anti-properdin mAb or when properdin was depleted from serum. Maximal AP-mediated C3 deposition on Neisseriae even at high (80%) serum concentrations required properdin. Consistent with prior observations, preincubation of bacteria with unfractionated properdin, followed by the addition of properdin-depleted serum resulted in higher C3 deposition than when bacteria were incubated with properdin-depleted serum alone. Unexpectedly, none of 10 Neisserial strains tested bound native properdin. Consistent with its inability to bind to Neisseriae, preincubating bacteria with native properdin followed by the addition of properdin-depleted serum did not cause detectable increases in C3 deposition. However, reconstituting properdin-depleted serum with native properdin a priori enhanced C3 deposition on all strains of Neisseria tested. In conclusion, the physiological forms of properdin do not bind directly to either N. meningitidis or N. gonorrhoeae but play a crucial role in augmenting AP-dependent C3 deposition on the bacteria through the "conventional" mechanism of stabilizing AP C3 convertases.

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    • "However it is possible that unfractionated properdin undergoing freeze thawing consists of high order oligomers of properdin, which may bind surfaces that native properdin would not (Farries et al., 1987). Agarwal et al. (2010), however, found that properdin does not bind directly to N. meningitidis or N. gonorrhoeae but enhances the deposition of C3 on the bacterial surface by stabilizing the alternative pathway C3 convertase. Another report has shown that native properdin (dimer, trimer, tetramer) binds to Chlamydia pneumonia. "
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    • "Recent studies have shown that properdin could also play a role in the initiation of alternative pathway complement activation, likely in an activating surface-and animal species–specific manner (Kemper, Atkinson, and Hourcade 2010; Hourcase 2006; Spitzer et al. 2007; Kimura et al. 2008; Agarwal et al. 2010; Ferreira, Cortes, and Pangburn 2010). Activated complement achieves its biological effect by promoting inflammation through the generation of C3a and C5a, referred to as anaphylatoxins, by opsonization of target cells or activating surfaces and by formation of the membrane attack complex (Dunkelberger and Song 2010a). "
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    • "Notably, properdin is a positive regulator of complement activation and this protein was shown to bind to the processed complement component C3 (C3b) [35] [36]. Both proteins are well known to interact with the bacterial cell surface, which supports our present study [37] [38] [39]. The C3b protein also interacts with complement factor B (fB), which was not identified in the present study. "
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