Differential effects of c-fms and c-kit ligands on the lineage development of the lymphohematopoietic cell line EML C1.
Differential effects of c-fms and c-kit ligands on the lineage development of the lymphohematopoietic cell line EML C1.
复制标题
c-fms 和 c-kit 配体对淋巴造血细胞系 EML C1 谱系发育的不同影响。
DOI：
10.1007/s002800051040
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发表时间：
1996
影响因子：
3
通讯作者：
Tsai,S
中科院分区：
文献类型：
--
作者：
Tsai,S
淋巴造血祖细胞占有核骨髓细胞的<0.01%。我们已经表明，小鼠淋巴造血祖细胞可以永生化的重组逆转录病毒载体窝藏显性负维甲酸（RA）受体。永生化的祖细胞作为干细胞因子依赖性克隆系增殖，命名为EML C1。EML C1细胞系自发产生前原B淋巴细胞以及红细胞和骨髓祖细胞。在用白细胞介素7和骨髓基质细胞刺激后，前原B淋巴细胞表达重组激活基因1（RAG-1）并经历免疫球蛋白重链基因的D-J重排。使用促红细胞生成素，红系祖细胞增殖并分化成红细胞。中性粒细胞和巨噬细胞的共同祖细胞[集落形成单位-粒细胞-巨噬细胞（CFU-GM）]的产生在EML C1细胞中受到抑制，但可被高浓度的RA诱导。在早幼粒细胞阶段发生了中性粒细胞分化的额外阻滞，但这也可以通过高浓度的RA克服。尽管c-fms与编码干细胞因子（SCF）受体的c-kit同源，但EML C1细胞既不表达c-fms，也不对c-fms的配体巨噬细胞集落刺激因子（M-CSF）应答。C-fmscDNA在EML C1细胞中的转导和表达赋予对M-CSF的响应性。这一发现表明，c-kit和c-fms共享基本上重叠的信号转导途径。然而，c-fms转导的EML C1细胞（EML C1/c-fms细胞）在单独用SCF或单独用M-CSF刺激时表现出不同的发育模式。当单独用SCF刺激时，EML C1/c-fms细胞主要显示红系和B淋巴样发育。当仅由M-CSF刺激时，发育转变为主要髓样（中性粒细胞和巨噬细胞）发育。这一观察结果表明，c-kit和c-fms必须有独特的信号转导途径，除了共同的。
The lymphohematopoietic progenitors represent <0.01% of nucleated marrow cells. We have shown that murine lymphohematopoietic progenitors can be immortalized by a recombinant retroviral vector harboring a dominant-negative retinoic acid (RA) receptor. The immortalized progenitors proliferate as a stem-cell factor-dependent clonal line designated EML C1. The EML C1 cell line spontaneously generates prepro-B-lymphocytes and erythroid and myeloid progenitors. Upon stimulation with interleukin 7 and marrow stromal cells, the prepro-B-lymphocytes express recombination-activating gene 1 (RAG-1) and undergo D-J rearrangements of the immunoglobulin heavy-chain genes. With erythropoietin, the erythroid progenitors proliferate and differentiate into red cells. Generation of the common progenitors for neutrophils and macrophages [colony-forming units-granulocyte-macrophage (CFU-GM)] is suppressed in EML C1 cells but is inducible by high concentrations of RA. An additional block in neutrophil differentiation occurs at the promyelocyte stage, but this can also be overcome by high concentrations of RA. Although c-fms is homologous to c-kit, which encodes the receptor for stem-cell factor (SCF), EML C1 cells neither express c-fms nor respond to macrophage colony-stimulating factor (M-CSF), the ligand for c-fms. Transduction and expression of c-fmscDNA in EML C1 cells confers responsiveness to M-CSF. This finding indicates that c-kit and c-fms share substantially overlapping signal-transduction pathways. However, c-fms-transduced EML C1 cells (EML C1/c-fms cells) exhibit different development patterns when stimulated by SCF alone or by M-CSF alone. When stimulated by SCF alone, EML C1/c-fms cells show mostly erythroid and B-lymphoid development. When stimulated by M-CSF alone, development switches to mostly myeloid (neutrophil and macrophage) development. This observation suggests that c-kit and c-fms must have unique signal-transduction pathways in addition to the common ones.