Sites of prion protein accumulation in scrapie‐infected mouse spleen revealed by immuno‐electron microscopy
Sites of prion protein accumulation in scrapie‐infected mouse spleen revealed by immuno‐electron microscopy
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DOI：
10.1002/1096-9896(200007)191:3
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发表时间：
2000-07
期刊：
影响因子：
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通讯作者：
M. Jeffrey;G. McGovern;C. Goodsir;Karen L Brown;M. Bruce
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文献类型：
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作者：
M. Jeffrey;G. McGovern;C. Goodsir;Karen L Brown;M. Bruce
与来自未感染脑的完全敏感的朊蛋白（PrPsen）相比，来自患有传染性海绵状脑病的动物脑的朊蛋白（PrP）是部分蛋白酶抗性的（PrPres）。在大多数实验模型中，PrPres是感染性的可靠指标。光学显微镜研究表明，PrPsen和PrP的疾病特异性积累都与滤泡树突状细胞（FDC）有关。使用免疫金电子显微镜，本研究证明了C57 BL小鼠脑内感染羊瘙痒病ME 7株后70天和疾病终末期170天的脾脏中PrP的疾病特异性蓄积。在这两个阶段，易染体巨噬细胞内的溶酶体和PrP也检测到在FDCs的质膜。在终末期病变小鼠卵泡的光区，所有FDC树突以高度反应性或增生性肾小球复合物的形式排列，其中PrP在FDC过程之间始终可见，与丰富的电子致密物质相关，解释为抗原-抗体复合物。在一些肾小球内，纤维状形式的PrP与淀粉样蛋白一致。在70天后的挑战，大或增生性的鸟氨酸复合物是罕见的，总是标记为PrP。然而，在此阶段，在简单的FDC工艺中也观察到稀疏的PrP标记。细胞外PrP在终末受影响小鼠脾脏中FDC的复杂肾小球树突中的普遍蓄积，与感染后70天小鼠中除少数FDC外的所有FDC中的简单FDC特征、稀疏PrP和有限的电子致密沉积形成对比。这表明，FDCs不断释放PrP从细胞表面，在那里它是与捕获的抗原抗体复合物和树突状延伸。这是可能的，易染体巨噬细胞获得PrP后，在iccosomes或从FDC树突周围的细胞外空间的PrP的吞噬。这些研究不支持FDC中PrP蓄积的细胞内阶段，但表明PrP由羊瘙痒病感染的细胞过量产生，并释放到细胞外空间。我们认为PrPsen参与树突状延伸或抗体-抗原捕获过程，可能是抗原-抗体复合物结合机制的一部分。© Crown copyright 2000.经英国政府文书局许可复制。由John Wiley & Sons有限公司出版
Prion protein (PrP) from the brains of animals with transmissible spongiform encephalopathies is partially protease resistant (PrPres) compared with fully sensitive PrP (PrPsen) from uninfected brains. In most experimental models, PrPres is a reliable indicator of infectivity. Light microscopic studies have suggested that both PrPsen and disease‐specific accumulations of PrP are associated with follicular dendritic cells (FDCs). Using immunogold electron microscopy, this study has demonstrated disease‐specific accumulation of PrP in the spleens of C57 BL mice, 70 days after intracerebral infection with the ME7 strain of scrapie and at the terminal stage of disease at 170 days. At both stages, tingible body macrophages contained PrP within lysosomes and PrP was also detected at the plasmalemma of FDCs. In the light zone of follicles of terminally diseased mice, all FDC dendrites were arranged in the form of highly reactive or hyperplastic labyrinthine glomerular complexes, within which PrP was consistently seen between FDC processes in association with abundant electron dense material, interpreted as antigen–antibody complexes. Within some glomeruli, fibrillar forms of PrP consistent with amyloid were seen. At 70 days after challenge, large or hyperplastic labyrinthine complexes were rare and invariably labelled for PrP. However, sparse PrP labelling was also seen on simple FDC processes at this stage. The ubiquitous accumulation of extracellular PrP in complex glomerular dendrites of FDCs in spleens from terminally affected mice, contrasted with simple FDC profiles, sparse PrP and limited electron dense deposits in all but a few FDCs of 70‐day post‐infected mice. This suggests that FDCs continually release PrP from the cell surface, where it is associated with trapped antigen–antibody complexes and dendritic extension. It is likely that tingible body macrophages acquire PrP following phagocytosis of PrP within iccosomes or from the extracellular space around FDC dendrites. These studies would not support an intracellular phase of PrP accumulation in FDCs but show that PrP is produced in excess by scrapie‐infected cells from where it is released into the extracellular space. We suggest that PrPsen is involved in dendritic extension or in the process of antibody–antigen trapping, perhaps as part of the binding mechanism for antigen–antibody complexes. © Crown copyright 2000. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.