MacGlashan Donald
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA
J Leukoc Biol. 2016 Sep;100(3):535-43. doi: 10.1189/jlb.2A0815-356R. Epub 2016 Mar 15.
In human basophils, Syk expression is 10-fold lower than most other types of leukocytes. There are indirect studies that suggest that Syk protein is highly unstable (a calculated half-life less than 15 min) in human peripheral blood basophils. Therefore, in these studies, Syk stability was directly examined. Purified basophils were metabolically labeled and a pulse-chase experimental design showed Syk protein to be stable in the time frame of 12 h (95% likelihood that half-life is more than 12 h). However, its synthetic rate was very slow (∼10-fold slower) compared with CD34-derived basophils, which have been shown to express levels of Syk consistent with other mature circulating leukocytes. Syk mRNA expression was found to be 5-30-fold lower than other cell types (CD34-derived basophils, peripheral blood eosinophils, and plasmacytoid dendritic cells). Syk protein and mRNA levels, across cell types, were relatively concordant. Syk mRNA in basophils showed a half-life of 3.5 h, which was greater than that of interleukin-4 or Fc epsilon receptor I-α mRNA (∼2 h), but somewhat shorter than Fc epsilon receptor I-β mRNA (8 h). A comparison of miR expression between CD34-derived and peripheral blood basophils demonstrated only 1 significant increase, in miR-150 (77-fold). Transfection in human embryonic kidney cells of a stabilized form of miR-150 showed that it modified expression of c-Myb mRNA but not of Syk mRNA or protein. These results suggest that low Syk expression in basophils results, not from protein instability and perhaps not from mRNA stability. Instead, the results point to the transcriptional nature of an important point of regulation.
在人类嗜碱性粒细胞中,Syk的表达水平比大多数其他类型的白细胞低10倍。有间接研究表明,Syk蛋白在人类外周血嗜碱性粒细胞中高度不稳定(计算得出的半衰期小于15分钟)。因此,在这些研究中,对Syk的稳定性进行了直接检测。纯化的嗜碱性粒细胞进行代谢标记,脉冲追踪实验设计表明Syk蛋白在12小时的时间范围内是稳定的(半衰期超过12小时的可能性为95%)。然而,与已被证明表达的Syk水平与其他成熟循环白细胞一致的CD34来源的嗜碱性粒细胞相比,其合成速率非常缓慢(约慢10倍)。发现Syk mRNA的表达比其他细胞类型(CD34来源的嗜碱性粒细胞、外周血嗜酸性粒细胞和浆细胞样树突状细胞)低5至30倍。跨细胞类型的Syk蛋白和mRNA水平相对一致。嗜碱性粒细胞中的Syk mRNA半衰期为3.5小时,长于白细胞介素-4或Fcε受体I-α mRNA(约2小时),但略短于Fcε受体I-β mRNA(8小时)。对CD34来源的嗜碱性粒细胞和外周血嗜碱性粒细胞之间的miR表达进行比较,仅发现miR-150有1个显著增加(77倍)。在人胚肾细胞中对稳定形式的miR-150进行转染表明,它改变了c-Myb mRNA的表达,但未改变Syk mRNA或蛋白的表达。这些结果表明,嗜碱性粒细胞中Syk表达低并非由于蛋白质不稳定,也许也不是由于mRNA稳定。相反,结果指向了一个重要调控点的转录性质。