Rosas Marcela, Gordon Siamon, Taylor Philip R
Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, UK.
Eur J Immunol. 2007 Sep;37(9):2518-28. doi: 10.1002/eji.200636892.
The granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine able to regulate a variety of cell functions including differentiation of macrophages and granulocytes, dendritic cell development and the maintenance of homeostasis. It binds specifically to its receptor, which is composed of a cytokine-specific alpha-chain (GM-CSF receptor alpha-chain, GMRalpha) and a beta-chain shared with the receptors for interleukin-3 and interleukin-5. In this report, we present a comprehensive study of GMRalpha in the mouse. We have found that the mouse GMRalpha is polymorphic and alternatively spliced. In the absence of specific antibodies, we generated a novel chimeric protein containing the Fc fragment of human IgG1 coupled to mouse GM-CSF, which was able to specifically bind to GMRalpha and induce proliferation of GMRalpha-transduced Ba/F3 cells. We used this reagent to perform the first detailed FACS study of the surface expression of mouse GMRalpha by leucocytes. Highest expression was found on monocytes and granulocytes, and variable expression on tissue macrophages. The GM-CSF receptor in mice is specifically expressed by myeloid cells and is useful for the detection of novel uncharacterised myeloid populations. The ability to detect GM-CSF receptor expression in experimental studies should greatly facilitate the analysis of its role in immune pathologies.
粒细胞-巨噬细胞集落刺激因子(GM-CSF)是一种造血细胞因子,能够调节多种细胞功能,包括巨噬细胞和粒细胞的分化、树突状细胞的发育以及体内稳态的维持。它特异性地结合其受体,该受体由细胞因子特异性α链(GM-CSF受体α链,GMRα)和与白细胞介素-3及白细胞介素-5受体共享的β链组成。在本报告中,我们对小鼠体内的GMRα进行了全面研究。我们发现小鼠GMRα具有多态性且存在可变剪接。在缺乏特异性抗体的情况下,我们构建了一种新型嵌合蛋白,该蛋白包含与小鼠GM-CSF偶联的人IgG1的Fc片段,它能够特异性结合GMRα并诱导GMRα转导的Ba/F3细胞增殖。我们使用该试剂对白细胞表面小鼠GMRα的表达进行了首次详细的荧光激活细胞分选(FACS)研究。在单核细胞和粒细胞上发现表达最高,而在组织巨噬细胞上表达各异。小鼠体内的GM-CSF受体在髓系细胞中特异性表达,可用于检测新的未表征的髓系细胞群体。在实验研究中检测GM-CSF受体表达的能力应能极大地促进对其在免疫病理中作用的分析。