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Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

Author

Listed:
  • David Weismann

    (Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences
    Medical University of Vienna)

  • Karsten Hartvigsen

    (Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences
    Medical University of Vienna
    University of California at San Diego)

  • Nadine Lauer

    (Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute and Friedrich Schiller University)

  • Keiryn L. Bennett

    (Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences)

  • Hendrik P. N. Scholl

    (Wilmer Eye Institute, Johns Hopkins University School of Medicine)

  • Peter Charbel Issa

    (Nuffield Laboratory of Ophthalmology, University of Oxford)

  • Marisol Cano

    (Wilmer Eye Institute, Johns Hopkins University School of Medicine)

  • Hubert Brandstätter

    (Medical University of Vienna
    Octapharma PPGmbH, Research & Development)

  • Sotirios Tsimikas

    (University of California at San Diego)

  • Christine Skerka

    (Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute and Friedrich Schiller University)

  • Giulio Superti-Furga

    (Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences)

  • James T. Handa

    (Wilmer Eye Institute, Johns Hopkins University School of Medicine)

  • Peter F. Zipfel

    (Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute and Friedrich Schiller University)

  • Joseph L. Witztum

    (University of California at San Diego)

  • Christoph J. Binder

    (Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences
    Medical University of Vienna
    University of California at San Diego)

Abstract

Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.

Suggested Citation

  • David Weismann & Karsten Hartvigsen & Nadine Lauer & Keiryn L. Bennett & Hendrik P. N. Scholl & Peter Charbel Issa & Marisol Cano & Hubert Brandstätter & Sotirios Tsimikas & Christine Skerka & Giulio , 2011. "Complement factor H binds malondialdehyde epitopes and protects from oxidative stress," Nature, Nature, vol. 478(7367), pages 76-81, October.
    • Handle: RePEc:nat:nature:v:478:y:2011:i:7367:d:10.1038_nature10449
    DOI: 10.1038/nature10449
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    Cited by:

    1. Chuchu Wan & Si He & Quanyong Cheng & Kehan Du & Yuhang Song & Xiang Yu & Hao Jiang & Caili Huang & Jiangping Xu & Cong Ma & Jintao Zhu, 2024. "Bridged emulsion gels from polymer–nanoparticle enabling large-amount biomedical encapsulation and functionalization," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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