Hudak S, Hunte B, Culpepper J, Menon S, Hannum C, Thompson-Snipes L, Rennick D
Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Blood. 1995 May 15;85(10):2747-55.
The effect of FLT3/FLK2 ligand (FL) on the growth of primitive hematopoietic cells was investigated using ThyloSca1+ stem cells. FL was observed to interact with a variety of factors to initiate colony formation by stem cells. When stem cells were stimulated in liquid culture with FL plus interleukin (IL)-3, IL-6, granulocyte colony-stimulating factor (G-CSF), or stem cell factor (SCF), cells capable of forming colonies in secondary methylcellulose cultures (CFU-c) were produced in high numbers. However, only FL plus IL-6 supported an increase in the number of cells capable of forming colonies in the spleens of irradiated mice (CFU-s). Experiments with accessory cell-depleted bone marrow (Lin- BM) showed that FL alone lacks significant colony-stimulating activity for progenitor cells. Nevertheless, FL enhanced the growth of granulocyte-macrophage progenitors (CFU-GM) in cultures containing SCF, G-CSF, IL-6, or IL-11. In these assays, FL increased the number of CFU-GM initiating colony formation (recruitment), as well as the number of cells per colony (synergy). Many of the colonies were macroscopic and contained greater than 2 x 10(4) granulocytes and macrophages. Therefore, FL appears to function as a potent costimulus for primitive cells of high proliferative potential (HPP). FL was also observed to costimulate the expansion of CFU-GM in liquid cultures of Lin- BM. In contrast, FL had no growth-promoting affects on progenitors committed to the erythrocyte, megakaryocyte, eosinophil, or mast cell lineages.
利用ThyloSca1+干细胞研究了FLT3/FLK2配体（FL）对原始造血细胞生长的影响。观察到FL与多种因子相互作用，启动干细胞的集落形成。当干细胞在液体培养中用FL加白细胞介素（IL）-3、IL-6、粒细胞集落刺激因子（G-CSF）或干细胞因子（SCF）刺激时，能够在二次甲基纤维素培养物中形成集落的细胞（CFU-c）大量产生。然而，只有FL加IL-6能使受照射小鼠脾脏中能够形成集落的细胞数量增加（CFU-s）。对去除辅助细胞的骨髓（Lin- BM）进行的实验表明，单独的FL对祖细胞缺乏显著的集落刺激活性。尽管如此，FL在含有SCF、G-CSF、IL-6或IL-11的培养物中增强了粒细胞-巨噬细胞祖细胞（CFU-GM）的生长。在这些试验中，FL增加了启动集落形成的CFU-GM数量（募集）以及每个集落中的细胞数量（协同作用）。许多集落肉眼可见，包含超过2×10⁴个粒细胞和巨噬细胞。因此，FL似乎作为高增殖潜能原始细胞（HPP）的有效共刺激因子发挥作用。还观察到FL在Lin- BM的液体培养中对CFU-GM的扩增具有共刺激作用。相比之下，FL对定向于红细胞、巨核细胞、嗜酸性粒细胞或肥大细胞谱系的祖细胞没有促生长作用。
