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* Department of Infection, Immunity and Inflammation and
Biomedical Services, University of Leicester, Leicester, United Kingdom; and
Institute of Immunology, University of Regensburg, Regensburg, Germany
Properdin is a positive regulator of complement activation so far known to be instrumental in the survival of infections with certain serotypes of Neisseria meningitidis. We have generated a fully backcrossed properdin-deficient mouse line by conventional gene-specific targeting. In vitro, properdin-deficient serum is impaired in alternative pathway-dependent generation of complement fragment C3b when activated by Escherichia coli DH5
. Properdin-deficient mice and wild-type littermates compare in their levels of C3 and IgM. In an in vivo model of polymicrobial septic peritonitis induced by sublethal cecal ligation and puncture, properdin-deficient mice appear immunocompromised, because they are significantly impaired in their survival compared with wild-type littermates. We further show that properdin localizes to mast cells and that properdin has the ability to directly associate with E. coli DH5
. We conclude that properdin plays a significant role in the outcome of polymicrobial sepsis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 The work was funded by the Medical Research Council (Grant G0400300 to C.M.S.), the Wellcome Trust (Grant 060574 to W.J.S.), and Deutsche Forschungsgemeinschaft (Grant MA760/10-3 to D.N.M).
2 Address correspondence and reprint requests to Dr. Cordula M. Stover, Department of Infection, Immunity and Inflammation, University of Leicester, University Road, Leicester LE1 9HN, U.K. E-mail address: cms13{at}le.ac.uk
3 Abbreviations used in this paper: CLP, cecal ligation and puncture; TSR, thrombospondin repeat; WT, wild type.
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