Junior Research Group Cellular Immunobiology, Leibniz Institute for Natural Product Research and Infection Biology, Jena 07745, Germany.
Biomolecules. 2012 Feb 7;2(1):46-75. doi: 10.3390/biom2010046.
Complement is an essential part of innate immunity as it participates in host defense against infections, disposal of cellular debris and apoptotic cells, inflammatory processes and modulation of adaptive immune responses. Several soluble and membrane-bound regulators protect the host from the potentially deleterious effects of uncontrolled and misdirected complement activation. Factor H is a major soluble regulator of the alternative complement pathway, but it can also bind to host cells and tissues, protecting them from complement attack. Interactions of factor H with various endogenous ligands, such as pentraxins, extracellular matrix proteins and DNA are important in limiting local complement-mediated inflammation. Impaired regulatory as well as ligand and cell recognition functions of factor H, caused by mutations or autoantibodies, are associated with the kidney diseases: atypical hemolytic uremic syndrome and dense deposit disease and the eye disorder: age-related macular degeneration. In addition, factor H binds to receptors on host cells and is involved in adhesion, phagocytosis and modulation of cell activation. In this review we discuss current concepts on the physiological and pathophysiological roles of factor H in light of new data and recent developments in our understanding of the versatile roles of factor H as an inhibitor of complement activation and inflammation, as well as a mediator of cellular interactions. A detailed knowledge of the functions of factor H in health and disease is expected to unravel novel therapeutic intervention possibilities and to facilitate the development or improvement of therapies.
补体是先天免疫系统的重要组成部分，它参与宿主对感染、细胞碎片和凋亡细胞的清除、炎症过程以及适应性免疫反应的调节。几种可溶性和膜结合的调节剂可防止宿主受到不受控制和定向错误的补体激活的潜在有害影响。因子 H 是替代补体途径的主要可溶性调节剂，但它也可以与宿主细胞和组织结合，保护它们免受补体攻击。因子 H 与各种内源性配体（如五聚蛋白、细胞外基质蛋白和 DNA）的相互作用对于限制局部补体介导的炎症非常重要。因子 H 的调节以及配体和细胞识别功能受损，由突变或自身抗体引起，与肾脏疾病有关：非典型溶血性尿毒症综合征和致密沉积物病以及眼部疾病：年龄相关性黄斑变性。此外，因子 H 与宿主细胞上的受体结合，并参与黏附、吞噬作用和细胞激活的调节。在这篇综述中，我们根据新数据和对因子 H 作为补体激活和炎症抑制剂以及细胞相互作用介导物的多功能作用的最新认识，讨论了因子 H 在生理和病理生理作用方面的当前概念。对因子 H 在健康和疾病中的功能的详细了解有望揭示新的治疗干预可能性，并促进治疗方法的开发或改进。
