RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR - EFFECTS ON NORMAL AND LEUKEMIC MYELOID CELLS
RECOMBINANT HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR - EFFECTS ON NORMAL AND LEUKEMIC MYELOID CELLS
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DOI：
10.1126/science.2420009
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发表时间：
1986-04-04
期刊：
影响因子：
56.9
通讯作者：
WELTE, K
中科院分区：
文献类型：
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作者：
SOUZA, LM;BOONE, TC;WELTE, K
本实验分离并鉴定了一种具有多能生物活性的人造血祖细胞集落刺激因子的基因和基因产物。该因子具有诱导小鼠单核细胞白血病细胞系WEHI-3B(D+)和新诊断的急性非淋巴细胞白血病(ANLL)患者细胞分化的能力。克隆了人多能粒细胞集落刺激因子(hG-CSF)基因的互补DNA拷贝，并在大肠杆菌中进行了表达。在CFU-GM检测中，重组形式的hG-CSF能够支持中性粒细胞的增殖。此外，重组人粒细胞集落刺激因子可支持早期红系集落和混合集落的形成。125I标记的HG-CSF与两例新诊断的人类白血病患者的细胞样本以及WEHI-3(D+)细胞的竞争结合研究表明，其中一种人类白血病(ANLL，归类为M4)和WEHI-3B(D)细胞具有HG-CSF的受体。此外，重组人粒细胞集落刺激因子可诱导小鼠WEHI-3B(D+)细胞和人白血病M2、M3、M4细胞向巨噬细胞和粒细胞终末分化。膀胱癌细胞株5637产生的分泌型蛋白质被发现是O-糖基化的，分子量为19,600。
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-3(D+) cells showed that one of the human leukemia (ANLL, classifed 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.