Souza L M, Boone T C, Gabrilove J, Lai P H, Zsebo K M, Murdock D C, Chazin V R, Bruszewski J, Lu H, Chen K K, Barendt J, Platzer E, Moore M A S, Mertelsmann R, Welte K
Science. 1986 Apr 4;232(4746):61-5. doi: 10.1126/science.2420009.
Experiments were conducted to isolate and characterize the gene and gene product of a human hematopoietic colony-stimulating factor with pluripotent biological activities. This factor has the ability to induce differentiation of a murine myelomonocytic leukemia cell line WEHI-3B(D+) and cells from patients with newly diagnosed acute nonlymphocytic leukemia (ANLL). A complementary DNA copy of the gene encoding a pluripotent human granulocyte colony-stimulating factor (hG-CSF) was cloned and expressed in Escherichia coli. The recombinant form of hG-CSF is capable of supporting neutrophil proliferation in a CFU-GM assay. In addition, recombinant hG-CSF can support early erythroid colonies and mixed colony formation. Competitive binding studies done with 125I-labeled hG-CSF and cell samples from two patients with newly diagnosed human leukemias as well as WEHI-3B(D+) cells showed that one of the human leukemias (ANLL, classified as M4) and the WEHI-3B(D+) cells have receptors for hG-CSF. Furthermore, the murine WEHI-3B(D+) cells and human leukemic cells classified as M2, M3, and M4 were induced by recombinant hG-CSF to undergo terminal differentiation to macrophages and granulocytes. The secreted form of the protein produced by the bladder carcinoma cell line 5637 was found to be O-glycosylated and to have a molecular weight of 19,600.
开展了实验以分离和鉴定一种具有多能生物活性的人造血集落刺激因子的基因及其基因产物。该因子能够诱导小鼠骨髓单核细胞白血病细胞系WEHI-3B(D+)以及新诊断的急性非淋巴细胞白血病（ANLL）患者的细胞发生分化。编码多能人类粒细胞集落刺激因子（hG-CSF）的基因的互补DNA拷贝被克隆并在大肠杆菌中表达。重组形式的hG-CSF在CFU-GM测定中能够支持中性粒细胞增殖。此外，重组hG-CSF能够支持早期红系集落和混合集落的形成。用125I标记的hG-CSF与两名新诊断的人类白血病患者以及WEHI-3B(D+)细胞的细胞样本进行的竞争性结合研究表明，其中一名人类白血病患者（ANLL，分类为M4）和WEHI-3B(D+)细胞具有hG-CSF受体。此外，重组hG-CSF可诱导分类为M2、M3和M4的小鼠WEHI-3B(D+)细胞和人类白血病细胞终末分化为巨噬细胞和粒细胞。发现膀胱癌细胞系5637产生的蛋白质的分泌形式为O-糖基化，分子量为19,600。
