Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

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 Superti-Furga, James T. Handa, Peter F. Zipfel, Joseph L. Witztum and Christoph J. Binder ()
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David Weismann: Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences
Karsten Hartvigsen: Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences
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
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

Nature, 2011, vol. 478, issue 7367, 76-81

Abstract: 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.

Date: 2011
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DOI: 10.1038/nature10449

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