Complement factor H binds malondialdehyde epitopes and protects from oxidative stress.
Complement factor H binds malondialdehyde epitopes and protects from oxidative stress.
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DOI：
10.1038/nature10449
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发表时间：
2011-10-05
期刊：
影响因子：
64.8
通讯作者：
Binder CJ
中科院分区：
文献类型：
--
作者：
Weismann D;Hartvigsen K;Lauer N;Bennett KL;Scholl HP;Charbel Issa P;Cano M;Brandstätter H;Tsimikas S;Skerka C;Superti-Furga G;Handa JT;Zipfel PF;Witztum JL;Binder CJ
氧化应激和脂质过氧化增强与许多慢性炎症性疾病有关，包括年龄相关性黄斑变性（AMD）。黄斑变性是西方社会致盲的主要原因，但其病因在很大程度上仍不清楚。丙二醛（MDA）是一种常见的脂质过氧化产物，在许多病理生理过程中积累，包括AMD。在这里，我们发现补体因子H （CFH）是一种主要的mda结合蛋白，可以阻断巨噬细胞对mda修饰蛋白的摄取，并在小鼠体内阻断mda诱导的促炎作用。与AMD密切相关的CFH多态性H402显著降低了CFH结合MDA的能力，表明与疾病病因有因果关系。我们的研究结果为氧化应激的先天免疫反应提供了重要的机制见解，这可能在AMD和其他慢性炎症性疾病的预防和治疗中被利用。
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.