Complement regulation in human atherosclerotic coronary lesions -: Immunohistochemical evidence that C4b-binding protein negatively regulates the classical complement pathway, and that C5b-9 is formed via the alternative complement pathway
Complement regulation in human atherosclerotic coronary lesions -: Immunohistochemical evidence that C4b-binding protein negatively regulates the classical complement pathway, and that C5b-9 is formed via the alternative complement pathway
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DOI：
10.1016/j.atherosclerosis.2006.06.013
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发表时间：
2007-05-01
期刊：
影响因子：
5.3
通讯作者：
Pentikainen, Markku O.
中科院分区：
文献类型：
--
作者：
Oksjoki, Riina;Kovanen, Petri T.;Pentikainen, Markku O.
目的：补体系统在人体动脉粥样硬化病变中被激活，可能因此加重局部炎症。我们研究了经典补体途径的主要抑制剂 C4b 结合蛋白 (C4bp) 在人类动脉粥样硬化病变中的存在和定位，与补体激活产物和蛋白 S 相关，后者与 C4bp 复合物循环。方法和结果：人类冠状动脉的免疫组织化学显示，C4bp 在正常动脉中几乎不存在，但存在于早期和晚期动脉粥样硬化病变中。在病变中，C4bp与蛋白聚糖相关，亲和层析显示C4bp与人动脉蛋白聚糖相互作用。含有 C4bp 的区域还含有 IgM 和 C4，表明 C4bp 参与经典补体途径的调节。然而，C5b-9 在这些区域中实际上不存在，而是与备解素共定位于内膜深处，表明 C5b-9 是由替代补体途径形成的。一小部分C4bp与蛋白S和凋亡细胞相关。结论：结果表明C4bp调节人动脉粥样硬化病变中的经典补体途径。因此，与旁路途径不同，经典补体途径不产生C5b-9，但可能参与清除动脉内膜中的凋亡细胞和细胞碎片。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
Objective: The complement system is activated in human atherosclerotic lesions and may hence aggravate local inflammation. We studied the presence and localization of C4b-binding protein (C4bp), the major inhibitor of the classical complement pathway, in human atherosclerotic lesions in relation to complement activation products and protein S, which circulates in complex with C4bp.Methods and results: Immunohistochemistry, of human coronary arteries showed C4bp to be virtually absent in normal arteries but present in early and advanced atherosclerotic lesions. In the lesions, C4bp is associated with proteoglycans, and affinity chromatography showed that C4bp interacts with human arterial proteoglycans. Areas containing C4bp also contained IgM and C4 suggesting that C4bp is involved in the regulation of the classical complement pathway. However, C5b-9 was virtually absent in these areas but, instead, colocalized with properdin deeper in the intima, suggesting that C5b-9 is formed by the alternative complement pathway. A fraction of C4bp was associated with protein S and apoptotic cells.Conclusions: The results indicate that C4bp regulates the classical complement pathway in human atherosclerotic lesions. Thus, unlike the alternative pathway, the classical complement pathway does not generate C5b-9, but is likely to be involved in the clean-up of apoptotic cells and cell debris in the arterial intima. (c) 2006 Elsevier Ireland Ltd. All rights reserved.