Complement activation and inflammatory processes in drusen formation and age related macular degeneration
Complement activation and inflammatory processes in drusen formation and age related macular degeneration
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DOI：
10.1006/exer.2001.1094
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发表时间：
2001-12-01
影响因子：
3.4
通讯作者：
Anderson, DH
中科院分区：
文献类型：
--
作者：
Johnson, LV;Leitner, WP;Anderson, DH
最近的研究表明炎症和补体介导的攻击是玻璃疣生物发生的早期事件。本文描述的研究试图确定是否可以在玻璃疣子结构内鉴定补体激活的主要位点，以及是否在玻璃疣和/或靠近玻璃疣的视网膜色素上皮（RPE）细胞中存在补体末端途径的已知抑制剂。免疫组织化学检查显示，玻璃体结合蛋白（Vn，S-蛋白）和簇蛋白（载脂蛋白J），是目前在玻璃疣的终端途径的两个液相调节剂：Vn也积累在与玻璃疣密切相关的RPE细胞的细胞质。膜相关补体抑制剂补体受体1也位于玻璃疣中。但在RPE细胞中未检测到。相反，第二种膜相关补体抑制剂膜辅因子蛋白。存在于玻璃疣相关的RPE细胞中。以及玻璃疣内的小的球形亚结构元件。这些先前未鉴定的元件还显示出对补体成分C3的蛋白水解片段的强免疫反应性，所述蛋白水解片段特征性地沉积在补体激活位点。提出这些结构代表来自退化的RPE细胞的残余碎片，所述RPE细胞是补体攻击的目标。可能的是，RPE细胞碎片截留在RPE单层和布鲁赫膜之间作为慢性炎症刺激和玻璃疣形成的潜在成核位点。因此，玻璃疣生物发生的过程可以被设想为原发性RPE病理的继发表现，其被局部炎症过程的后果加重。(C)北京：科学出版社.
Recent studies implicate inflammation and complement mediated attack as early events in drusen biogenesis. The investigations described here sought to determine whether primary sites of complement activation could be identified within drusen substructure, and whether known inhibitors of the terminal pathway of complement are present in drusen and/or retinal pigmented epithelial (RPE) cells that lie in close proximity to drusen. Inummohistochemical examination shows two fluid phase regulators of the terminal pathway, vitronectin (Vn, S-protein) and clusterin (apolipoprotein J), to be present in drusen: Vn also accumulates in the cytoplasm of RPE cells that are closely associated with drusen. The membrane associated complement inhibitor, complement receptor 1, is also localized in drusen. but it is not detected in RPE cells immunohistochemically. In contrast, a second membrane associated complement inhibitor, membrane cofactor protein. is present in drusen associated RPE cells. as well as in small, spherical substructural elements within drusen. These previously unidentified elements also show strong immunoreactivity for proteolytic fragments of complement component C3 that are characteristically deposited at sites of complement activation. it is proposed that these structures represent residual debris from degenerating RPE cells that are the targets of complement attack. It is likely that RPE cell debris entrapped between the RPE monolayer and Bruch's membrane serves as a chronic inflammatory stimulus and a potential nucleation site for drusen formation. Thus, the process of drusen biogenesis may be envisaged as a secondary manifestation of primary RPE pathology that is exacerbated by consequences of local inflammatory processes. (C) 2001 Academic Press.