Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease

Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease
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DOI:
10.1006/exnr.1997.6738
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发表时间:
1998-02-01
影响因子:
5.3
通讯作者:
Silver, J
Silver, J
中科院分区:
医学2区
文献类型:
--
作者:
DeWitt, DA;Perry, G;Silver, J

文献摘要

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我们建立了一种将分离的老年斑(SP)核呈现给培养的大鼠小胶质细胞的体外模型。小胶质细胞迅速吞噬、裂解和清除SP核心。然而,当与星形胶质细胞共培养时,小胶质细胞的吞噬功能明显受到抑制,从而使SPS得以持续存在。抑制星形胶质细胞的吞噬作用似乎是一种普遍现象,因为在星形胶质细胞存在的情况下,小胶质细胞对吞噬乳胶珠的能力也降低。星形胶质细胞对小胶质细胞的作用部分与一种扩散因子(S)有关,因为星形胶质细胞条件培养液(而不是成纤维细胞条件培养液)也减少吞噬。这些结果表明,虽然小胶质细胞具有吞噬和清除SP的能力,但与小胶质细胞密切相关的星形胶质细胞可能有助于阻止SP物质的有效清除,从而使它们在阿尔茨海默病中持续存在。(C)1998年学术出版社。
We have developed an in vitro model in which isolated senile plaque (SP) cores are presented to rat microglial cells in culture. Microglia rapidly phagocytosed, broke apart, and cleared SP cores. However, when cocultured with astrocytes, microglial phagocytosis was markedly suppressed, allowing the SPs to persist. Suppression of phagocytosis by astrocytes appears to be a general phenomena since microglia in the presence of astrocytes showed reduced capacity to phagocytose latex beads as well. The astrocyte effect on microglia is related in part to a diffusible factor(s) since astrocyte-but not fibroblast-conditioned media also reduced phagocytosis. These results suggest that while microglia have the capacity to phagocytose and remove SPs, astrocytes which lie in close association to microglia may help prevent the efficient clearance of SP material allowing them to persist in Alzheimer's disease. (C) 1998 Academic Press.