Schumann R R, Nakarai T, Gruss H J, Brach M A, von Arnim U, Kirschning C, Karawajew L, Ludwig W D, Renauld J C, Ritz J, Herrmann F
Department of Medical Oncology and Applied Molecular Biology, Virchow Klinikum der Humboldt Universität Berlin, Germany.
Blood. 1996 Mar 15;87(6):2419-27.
Expression of the interleukin-2 receptor alpha-(IL-2Ralpha-), IL-2Rbeta-, and the recently identified IL-2Rgamma-chain was examined on a wide range of cells of myeloid origin including neutrophils, monocytes, normal bone marrow-derived myeloid progenitors enriched for CD34+ cells, bone marrow blasts obtained from acute myelogenous leukemia (AML) patients, and permanent myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction and surface membrane analysis using receptor chain-specific monoclonal antibodies and flow cytometry. Expression of the p75 IL-2Rbeta- and the p64 IL-2Rgamma-chain was a common finding in most of the myeloid cell samples investigated, whereas IL-2Ralpha-chain was less frequently expressed. Although the high-affinity IL-2R form (ie, the alpha+, beta+, gamma+ IL-2R form) was detectable in a small minority of primary AML samples as well as the KG-1 cell line and IL-2 binding to these cells was sufficient to initiate signal transduction as evidenced by an increase in overall protein tyrosine phosphorylation and more specifically in tyrosine phosphorylation of the Janus kinase (JAK) 3, in none of these cell types did exposure to IL-2 affect cell growth kinetics. These results suggest that, in myeloid cells, the IL-2R may not stimulate mitogenic responses or that its components may be expressed in a combinational association with receptors for other cytokines and that IL-2Rgamma may play a regulatory role in normal and malignant myelopoiesis possibly independent from IL-2. Because recent studies by others have indicated that the IL-2Rgamma- chain may be shared by the IL-4R, the IL-7R, and most likely the IL-9R, expression of mRNA of these receptor types was also investigated in these cell samples. Surprisingly, in a substantial part of the myeloid lineage cells examined, an IL-2Rgamma+, IL-4R-, IL7R- configuration was noted that was, however, frequently associated with expression of IL-9R. Sharing of IL-9R/IL-2R components was furthermore suggested by inhibition of 125I-IL-2 binding to primary AML cells with excess of unlabeled IL-9.
通过逆转录聚合酶链反应以及使用受体链特异性单克隆抗体和流式细胞术进行表面膜分析，检测了白细胞介素2受体α链（IL-2Rα）、IL-2Rβ链和最近鉴定出的IL-2Rγ链在多种髓系来源细胞上的表达，这些细胞包括中性粒细胞、单核细胞、富集CD34+细胞的正常骨髓来源髓系祖细胞、急性髓性白血病（AML）患者的骨髓原始细胞以及永久性髓系白血病细胞系。在所研究的大多数髓系细胞样本中，常见p75 IL-2Rβ链和p64 IL-2Rγ链的表达，而IL-2Rα链的表达则较少见。尽管在少数原发性AML样本以及KG-1细胞系中可检测到高亲和力IL-2R形式（即α+、β+、γ+ IL-2R形式），并且IL-2与这些细胞的结合足以启动信号转导，这可通过总蛋白酪氨酸磷酸化增加，更具体地说是通过Janus激酶（JAK）3的酪氨酸磷酸化增加来证明，但在这些细胞类型中，暴露于IL-2均未影响细胞生长动力学。这些结果表明，在髓系细胞中，IL-2R可能不会刺激有丝分裂反应，或者其组分可能与其他细胞因子的受体以组合形式表达，并且IL-2Rγ可能在正常和恶性髓系造血中发挥调节作用，可能独立于IL-2。因为其他人最近的研究表明IL-2Rγ链可能为IL-4R、IL-7R所共有，并且很可能也为IL-9R所共有，所以也在这些细胞样本中研究了这些受体类型的mRNA表达。令人惊讶的是，在所检查的大部分髓系谱系细胞中，发现了一种IL-2Rγ+、IL-4R-、IL-7R-的构型，然而，这种构型经常与IL-9R的表达相关。用过量未标记的IL-9抑制125I-IL-2与原发性AML细胞的结合，进一步提示了IL-9R/IL-2R组分的共享。
