Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood
Elevation of the terminal complement activation products C5a and C5b-9 in ALS patient blood
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DOI：
10.1016/j.jneuroim.2014.09.005
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发表时间：
2014-11-15
影响因子：
3.3
通讯作者：
Woodruff, T. M.
中科院分区：
文献类型：
--
作者：
Mantovani, S.;Gordon, R.;Woodruff, T. M.
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种以中枢神经系统运动神经元进行性丧失为特征的神经退行性疾病。神经变性和炎症过程，包括补体系统的激活是这种病理学的标志。我们过去在ALS动物模型（hSOD 1（G93 A）啮齿动物）中的工作揭示了补体激活片段C5 a（C5 aR）受体的阻断改善了ALS样症状并延长了存活。我们现在表明，与健康对照组相比，ALS患者血浆中C5 a和C5 b-9的水平显著升高，但C3 a和C4 a均未升高。ALS患者的白细胞内C5 a也升高，表明C5 a受体相互作用增强。总体而言，这些发现表明ALS中存在增强的外周免疫补体末端途径激活，这可能与疾病过程相关。(C)2014爱思唯尔有限公司版权所有。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized by the progressive loss of motor neurons within the central nervous system. Neural degeneration and inflammatory processes, including activation of the complement system are hallmarks of this pathology. Our past work in ALS animal models (hSOD1(G93A) rodents) has revealed that blockade of the receptor for complement activation fragment C5a (C5aR), improves ALS-like symptoms and extends survival. We now show that the levels of C5a and C5b-9, but not C3a nor C4a, are significantly elevated in plasma from ALS patients compared to healthy controls. C5a was also elevated within leukocytes from ALS patients suggesting heightened C5a receptor interaction. Overall, these findings indicate that there is enhanced peripheral immune complement terminal pathway activation in ALS, which may have relevance in the disease process. (C) 2014 Elsevier B.V. All rights reserved.