von Wussow P, Jakschies D, Hochkeppel H K, Fibich C, Penner L, Deicher H
Department of Immunology and Transfusion Medicine, Medical School of Hannover, FRG.
Eur J Immunol. 1990 Sep;20(9):2015-9. doi: 10.1002/eji.1830200920.
The murine Mx-1 protein is one of the best biochemically and functionally characterized interferon (IFN)-induced proteins that is necessary, and sufficient, for providing resistance to murine cells against viral influenza infection. Recently an intracellular human protein homologous to the murine Mx-1 protein has been identified by means of a specific monoclonal antibody. The restricted induction of this intracellular protein in human mononuclear cells (MNC) by various cytokines was investigated. MNC from 26 of 28 healthy people and 35 of 36 cancer patients before IFN-alpha therapy had no detectable Mx-homologous protein. Incubation of human MNC with IFN-alpha and IFN-beta for 24 h at different concentrations led to a dose-dependent induction of the Mx-homologous protein. All IFN-alpha or IFN-beta preparations tested were equally effective in eliciting this intracellular protein. IFN-gamma induced only 1% of the Mx amount elicited by type-1 IFN compared on a weight basis. Neither interleukin (IL) 1 nor IL3, IL4, IL5, IL6, tumor necrosis factor-alpha/beta, granulocyte colony-stimulating factor (CSF) or granulocyte macrophage-CSF at any of the concentrations tested were capable of eliciting any detectable amount of the Mx homolog, while IL2 was a poor Mx-homologous protein inducer. In the presence of high-titered IFN-alpha antisera both IL2 and IFN-gamma were unable to stimulate this protein, proving that IFN-gamma and IL2 indirectly induce the Mx homolog via IFN-alpha. Therefore, the human Mx-homologous protein is a strictly by type I IFN-regulated protein in human peripheral blood lymphocytes.
小鼠Mx-1蛋白是干扰素（IFN）诱导产生的、生化特性和功能特征最为明确的蛋白之一，它对于小鼠细胞抵抗甲型流感病毒感染是必需且充分的。最近，借助一种特异性单克隆抗体，人们鉴定出一种与小鼠Mx-1蛋白同源的细胞内人类蛋白。研究了多种细胞因子对人单核细胞（MNC）中这种细胞内蛋白的诱导作用。28名健康人中的26名以及36名癌症患者中35名在接受α-干扰素治疗前，其MNC中均未检测到Mx同源蛋白。用不同浓度的α-干扰素和β-干扰素与人MNC孵育24小时，会导致Mx同源蛋白呈剂量依赖性诱导产生。所有测试的α-干扰素或β-干扰素制剂在诱导这种细胞内蛋白方面同样有效。相比之下，γ-干扰素诱导产生的Mx量仅为1型干扰素诱导量的1%（按重量计算）。在所测试的任何浓度下，白细胞介素（IL）-1、IL-3、IL-4、IL-5、IL-6、肿瘤坏死因子-α/β、粒细胞集落刺激因子（CSF）或粒细胞巨噬细胞-CSF均无法诱导产生任何可检测量的Mx同源物，而IL-2是一种较弱的Mx同源蛋白诱导剂。在存在高滴度α-干扰素抗血清的情况下，IL-2和γ-干扰素均无法刺激这种蛋白，这证明γ-干扰素和IL-2是通过α-干扰素间接诱导Mx同源物的。因此，人Mx同源蛋白是人类外周血淋巴细胞中严格受I型干扰素调节的蛋白。
