Cited by 533Complement system in diseasesRetinal Diseases and TreatmentsAntioxidant Activity and Oxidative Stress

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Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

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Weismann, David, Hartvigsen, Karsten, Lauer, Nadine, Bennett, Keiryn L., Scholl, Hendrik P. N., Issa, Peter Charbel, Cano, Marisol, Brandstätter, Hubert, Tsimikas, Sotirios, Skerka, Christine, Superti-Furga, Giulio, Handa, James T., Zipfel, Peter F., Witztum, Joseph L., Binder, Christoph J.·2011·Nature

DOI 10.1038/nature10449PMC PMC4826616

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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.

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Background
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Background
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Background
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Background
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Background
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Background
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BackgroundMethodInfluential
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BackgroundInfluential
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Background
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Background
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Background
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Background
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Authors: Weismann, D., Hartvigsen, K., Lauer, N., Bennett, K. L., Scholl, H. P. N., Issa, P. C., Cano, M., Brandstätter, H., Tsimikas, S., Skerka, C., Superti-Furga, G., Handa, J. T., Zipfel, P. F., Witztum, J. L., & Binder, C. J.
Affiliations: Austrian Academy of Sciences (AT)
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
Johns Hopkins University (US)
University of Oxford (GB)
Octapharma (Austria) (AT)
University of California San Diego (US)
Corresponding author: Binder, Christoph J.
ORCID: Bennett, Keiryn L.
Scholl, Hendrik P. N.
Issa, Peter Charbel
Tsimikas, Sotirios
Skerka, Christine
Handa, James T.
Zipfel, Peter F.
Witztum, Joseph L.
Binder, Christoph J.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2011-10
Volume: 478
Issue: 7367
Pages: 76-81
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10449
PMC: PMC4826616
OpenAlex: W2062097745
Cited by: 533
References: 42
Citations by year: 2026: 16 · 2025: 24 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 42 · 2020: 36 · 2019: 29 · 2018: 33 · 2017: 31 · 2016: 39 · 2015: 42 · 2014: 44 · 2013: 66 · 2012: 44
FWCI: 22.28
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: National Heart, Lung, and Blood Institute (R01-HL086599, HL-088093, P01HL088093)
National Eye Institute (EY14005, R01EY014005, EY019044, R01EY019904)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
Keywords: complement factor H, malondialdehyde, lipid peroxidation, oxidative stress, age-related macular degeneration, macrophage uptake, pro-inflammatory effects, innate immunity, chronic inflammation, retina
MeSH terms: Animals, Epitopes, Binding Sites, Complement System Proteins, Complement Inactivator Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Macular Degeneration, Male, Malondialdehyde, Mice, Inbred C57BL, Mutation, Necrosis, Protein Binding, Retina, Lipid Peroxidation, Apoptosis, Complement Factor H, Protein Structure, Tertiary, Macrophages, Peritoneal, Oxidative Stress, Mice

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Complement factor H binds malondialdehyde epitopes and protects from oxidative stress

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