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阿尔茨海默病中膜攻击复合物C5b - 9的分子与细胞特征

Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease.

作者信息

Webster S, Lue L F, Brachova L, Tenner A J, McGeer P L, Terai K, Walker D G, Bradt B, Cooper N R, Rogers J

机构信息

Department of Molecular Biology and Biochemistry, University of California, Irvine 92697, USA.

出版信息

Neurobiol Aging. 1997 Jul-Aug;18(4):415-21. doi: 10.1016/s0197-4580(97)00042-0.

DOI:10.1016/s0197-4580(97)00042-0
PMID:9330973
Abstract

The membrane attack complex, C5b-9, is of considerable importance in many inflammatory reactions. It is the terminal, cytolytic component of both classical and alternative pathway activation, and its presence presupposes other potentially destructive complement constituents, including anaphylotoxins and opsonins. We have characterized C5b-9 and its C9 constituent in the Alzheimer's disease (AD) and nondemented elderly (ND) brain using immunohistochemistry at the light and electron microscopic levels, Western blot analysis, and the reverse transcriptase polymerase chain reaction. We have also conducted in vitro ELISA assays of amyloid beta-peptide-stimulated SC5b-9 production. C5b-9 is abundantly present in Alzheimer's disease cortex, associated with neurofibrillary tangle containing neurons, dystrophic neurites within neuritic plaques, and neuropil threads, but is weakly detected, if at all, in nondemented elderly cortex under the same conditions. Staining of Alzheimer's disease sections is abolished both by deletion of primary antibody or preabsorption with purified SC5b-9.

摘要

膜攻击复合物C5b-9在许多炎症反应中具有相当重要的意义。它是经典途径和替代途径激活的终末溶细胞成分,其存在意味着存在其他潜在的具有破坏性的补体成分,包括过敏毒素和调理素。我们利用光镜和电镜水平的免疫组织化学、蛋白质印迹分析以及逆转录聚合酶链反应,对阿尔茨海默病(AD)和非痴呆老年人(ND)大脑中的C5b-9及其C9成分进行了表征。我们还进行了体外ELISA检测,以检测淀粉样β肽刺激下的SC5b-9生成情况。C5b-9大量存在于阿尔茨海默病皮质中,与含有神经原纤维缠结的神经元、神经炎性斑块内的营养不良性神经突以及神经毡丝相关,但在相同条件下,在非痴呆老年人皮质中即使能检测到也很微弱。通过缺失一抗或用纯化的SC5b-9预吸附,阿尔茨海默病切片的染色均被消除。

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