Clusterin expression in follicular dendritic cells associated with prion protein accumulation
Clusterin expression in follicular dendritic cells associated with prion protein accumulation
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DOI：
10.1002/path.2009
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发表时间：
2006-08-01
影响因子：
7.3
通讯作者：
Iwaki, T.
中科院分区：
文献类型：
--
作者：
Sasaki, K.;Doh-ura, K.;Iwaki, T.
在变异型Creutzfeldt-Jakob病和一些传染性海绵状脑病（TSE）动物模型中，异常朊蛋白（PrP）的外周蓄积可能发生在淋巴网状系统中。在淋巴组织内，异常PrP积聚发生在滤泡树突状细胞（FDC）上。丛生蛋白（载脂蛋白J）已被认为是与TSEs中PrP相关的分子之一，并且丛生蛋白在发生异常PrP沉积的中枢神经系统中表达增加。因此，我们研究了外周clusterin表达的背景下，在一系列的人类和实验TSE的FDCs上的PrP积累。使用一种新的高灵敏度的方法，涉及洗涤剂高压灭菌预处理的组织切片上检测PrP。树突状网络模式的clusterin免疫反应在淋巴滤泡中观察到与异常的PrP对FDCs。clusterin免疫反应性的增加似乎与PrP沉积的程度，无论病原体菌株，宿主小鼠品系或各种免疫修饰。这些蛋白的共定位和相关表达表明clusterin可能与PrP异常直接相关。事实上，与PrP相关的丛生蛋白免疫反应性在FDC耗尽后保留。总之，这些数据表明，clusterin可能作为一个伴侣样分子的PrP和TSE发病机制中发挥重要作用。版权所有（c）2006大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Peripheral accumulation of abnormal prion protein (PrP) in variant Creutzfeldt-Jakob disease and some animal models of transmissible spongiform encephalopathies (TSEs) may occur in the lymphoreticular system. Within the lymphoid tissues, abnormal PrP accumulation occurs on follicular dendritic cells (FDCs). Clusterin (apolipoprotein J) has been recognized as one of the molecules associated with PrP in TSEs, and clusterin expression is increased in the central nervous system where abnormal PrP deposition has occurred. We therefore examined peripheral clusterin expression in the context of PrP accumulation on FDCs in a range of human and experimental TSEs. PrP was detected immunohistochemically on tissue sections using a novel highly sensitive method involving detergent autoclaving pretreatment. A dendritic network pattern of clusterin immunoreactivity in lymphoid follicles was observed in association with the abnormal PrP on FDCs. The increased clusterin immunoreactivity appeared to correlate with the extent of PrP deposition, irrespective of the pathogen strains, host mouse strains or various immune modifications. The observed co-localization and correlative expression of these proteins suggested that clusterin might be directly associated with abnormal PrP. Indeed, clusterin immunoreactivity in association with PrP was retained after FDC depletion. Together these data suggest that clusterin may act as a chaperone-like molecule for PrP and play an important role in TSE pathogenesis. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.