The expression and potential function of cellular prion protein in human lymphocytes

The expression and potential function of cellular prion protein in human lymphocytes
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DOI:
10.1006/cimm.2000.1751
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发表时间:
2001-01-10
影响因子:
4.3
通讯作者:
Sy, MS
Sy, MS
中科院分区:
医学4区
文献类型:
--
作者:
Li, RL;Liu, DC;Sy, MS

文献摘要

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我们研究了正常细胞朊蛋白(PrPC)在人外周血单核细胞(PBMC)和转染的神经母细胞瘤细胞与一组六个单克隆抗体(Mab)的表达。虽然所有六种Mab都与神经母细胞瘤细胞强烈反应,但只有四种Mab与人PBMC表达的PrPC反应,PrPC在人T细胞、B细胞、单核细胞和树突细胞中以高水平表达,但在红细胞中不表达。免疫印迹研究表明,PrPC糖的形式和在人PBMC中的PrPC上的N-连接的聚糖的组成不同于脑或神经母细胞瘤细胞的那些。在人PBMC和神经母细胞瘤细胞系中,PrPC的N-末端部分对蛋白水解消化高度敏感,这表明活细胞表面上的PrPC的N-末端缺乏二级结构。我们发现,作为细胞活化的结果,人T淋巴细胞表面上表达的PrPC水平上调。因此,记忆T细胞比初始T细胞表达更多的PrPC。此外,抗PrPC单克隆抗体抑制用抗CDS单克隆抗体刺激的人T淋巴细胞的增殖。总的来说,这些结果表明PrPC可以参与人T淋巴细胞中的信号转导,(C)2001学术出版社。
We examined expression of the normal cellular prion protein (PrPC) in human peripheral blood mono-nuclear cells (PBMC) and in transfected neuroblastoma cells with a panel of six monoclonal antibodies (Mabs). While all six of the Mabs reacted strongly with the neuroblastoma cells, only four of the Mabs reacted with PrPC expressed by human PBMC, PrPC is expressed at high levels in human T cells, B cells, monocytes, and dendritic cells, but not in red blood cells. Immunoblotting studies revealed that the PrPC glyco-forms and the composition of the N-linked glycans on PrPC in human PBMC are different from those of the brain or the neuroblastoma cells. In human PBMC and the neuroblastoma cell lines the N-terminal portion of the PrPC is hypersensitive to proteolytic digestion, suggesting that the N-terminus of the PrPC on the surface of a living cell lacks secondary structure. We found that the level of PrPC expressed on the surface of human T lymphocytes was up-regulated as a consequence of cellular activation. Accordingly, memory T cells express more PrPC than naive T cells. In addition, the proliferation of human T lymphocytes stimulated with an anti-CDS Mab was inhibited by anti-PrPC Mabs, Collectively, these results suggest that PrPC can participate in signal transduction in human T lymphocytes, (C) 2001 Academic Press.