Zhou Haiyun, Zhou Xiangmei, Kouadir Mohammed, Zhang Zhongqiu, Yin Xiaomin, Yang Lifeng, Zhao Deming
National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
J Neurosci Methods. 2009 Jun 30;181(1):1-5. doi: 10.1016/j.jneumeth.2009.04.002. Epub 2009 Apr 14.
Prion diseases are characterized by accumulation of protease resistant isoforms of prion protein (PrP), and infiltration and activation of mononuclear phagocytes at the brain lesions. Interactions between prion proteins and immune cells during disease progression are still not very well understood. In the present study, multiwell chamber chemotaxis assay was carried out to assess the migratory response of macrophage cell line Ana-1 to a synthetic peptide homologous to residues 106-126 of the human prion protein. Specific protein kinase inhibitors were used to elucidate the signaling events underlying PrP106-126-induced macrophages migration, and a comparison with the signaling pattern of macrophage migration induced by substance P (SP) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), respectively, was carried out. The results showed that PrP106-126 had a potent chemotactic effect on murine macrophage cell line Ana-1; that multiple signaling pathways might be involved in the PrP106-126-induced macrophage migrations; and that PrP106-126-induced chemotactic activity was similar to that induced by SP. These findings provide new insights into the mechanisms underlying the interaction between PrP and macrophages.
朊病毒疾病的特征是朊病毒蛋白（PrP）的蛋白酶抗性异构体的积累，以及脑损伤处单核吞噬细胞的浸润和激活。在疾病进展过程中，朊病毒蛋白与免疫细胞之间的相互作用仍未得到很好的理解。在本研究中，进行了多孔板趋化性测定，以评估巨噬细胞系Ana-1对与人朊病毒蛋白106-126位残基同源的合成肽的迁移反应。使用特异性蛋白激酶抑制剂来阐明PrP106-126诱导巨噬细胞迁移的信号转导事件，并分别与P物质（SP）和N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）诱导的巨噬细胞迁移的信号模式进行比较。结果表明，PrP106-126对小鼠巨噬细胞系Ana-1具有强大的趋化作用；PrP106-126诱导的巨噬细胞迁移可能涉及多种信号通路；并且PrP106-126诱导的趋化活性与SP诱导的趋化活性相似。这些发现为PrP与巨噬细胞相互作用的机制提供了新的见解。
