Role of cell death in the propagation of PrPSc in immune cells

Role of cell death in the propagation of PrPSc in immune cells
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细胞死亡在免疫细胞中 PrPSc 增殖中的作用

DOI:
10.1007/s00705-014-2320-z
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发表时间:
2015
影响因子:
2.7
通讯作者:
N.
N.
中科院分区:
医学4区
文献类型:
--
作者:
Takahashi;K.;Inoshima;Y.;Ishiguro;N.

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许多研究表明,巨噬细胞,树突状细胞和滤泡树突状细胞在PrPSc的繁殖中发挥重要作用。PrPSchave在外周巨噬细胞中的蓄积和蛋白水解均被证实。如果细胞在瞬时PrPSc传播过程中死亡,则巨噬细胞可作为PrPSc颗粒的储存库。然而,细胞死亡是否在巨噬细胞中的PrPSc增殖中起作用仍不清楚。在这项研究中,我们调查了传播和传播的死亡免疫细胞和活的神经细胞之间的PrPSc的可能性。我们发现,在特定条件下,瞬时PrPSc繁殖发生在死细胞中,表明PrPC和PrPScon质膜脂筏之间的相互作用可能是重要的PrPSc繁殖。与受体N2 a-3神经母细胞瘤细胞共培养灭活供体PrPSc感染的巨噬细胞加速PrPSc传递。我们的研究结果表明,细胞死亡可能在PrPSc传播中起重要作用,而瞬时PrPSc在巨噬细胞中的传播对PrPSc的传递几乎没有影响。
A number of studies have suggested that macrophages, dendritic cells, and follicular dendritic cells play an important role in the propagation of PrPSc. Both accumulation and proteolysis of PrPSchave been demonstrated in peripheral macrophages. Macrophages may act as reservoirs for PrPScparticles if the cells die during transient PrPScpropagation. However, whether cell death plays a role in PrPScpropagation in macrophages remains unclear. In this study, we investigated the possibility of propagation and transmission of PrPScbetween dead immune cells and living neural cells. We found that under specific conditions, transient PrPScpropagation occurs in dead cells, indicating that interaction between PrPCand PrPScon plasma membrane lipid rafts might be important for PrPScpropagation. Co-culturing of killed donor PrPSc-infected macrophages with recipient N2a-3 neuroblastoma cells accelerated PrPSctransmission. Our results suggest that cell death may play an important role in PrPScpropagation, whereas transient PrPScpropagation in macrophages has little effect on PrPSctransmission.
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