McKenna H J, de Vries P, Brasel K, Lyman S D, Williams D E
Immunex Corp, Seattle, WA 98101, USA.
Blood. 1995 Nov 1;86(9):3413-20.
A ligand for the tyrosine kinase receptor flt3/flk-2, referred to here as flt3 ligand (flt3L), was recently cloned. The effect of flt3L on purified human CD34+ progenitor cells was examined. flt3 receptor (flt3R) was detected on the surface of human bone marrow cells that were enriched for CD34 expression. The effects of flt3L and the c-kit ligand Steel factor (SLF) on hematopoietic progenitors were compared in clonal colony assays. Both factors synergized with Pixy321 (interleukin-3 [IL-3]-granulocyte-macrophage colony-stimulating factor fusion protein) to induce granulocytic-monocytic (GM) and high proliferative potential (HPP) colonies and synergized with Pixy321 + erythropoietin (EPO) to induce multipotent granulocytic-erythroid-monocytic-megakaryocytic colonies. Although SLF had a potent effect on colony formation of erythroid restricted progenitor cells (burst-forming unit-erythroid), no effect by flt3L was observed. The addition of flt3L to irradiated long-term marrow cultures seeded with CD34+ cells augmented both total and progenitor cell production. Ex vivo expansion studies with isolated CD34+ bone marrow cells from normal donors showed that flt3L alone supported maintenance of both GM and HPP progenitors for 3 to 4 weeks in vitro. The addition of flt3L to a growth factor combination of IL-1 alpha + IL-3 + IL-6 + EPO resulted in a synergistic effect on progenitor cell expansion comparable to that observed with the addition of SLF to IL-1 alpha + IL-3 + IL-6 + EPO. These data show a function for flt3L in the regulation of both primitive multipotent and lineage-committed hematopoietic progenitor cells.
一种酪氨酸激酶受体flt3/flk-2的配体，本文称为flt3配体（flt3L），最近已被克隆。研究了flt3L对纯化的人CD34+祖细胞的作用。在富含CD34表达的人骨髓细胞表面检测到了flt3受体（flt3R）。在克隆集落测定中比较了flt3L和c-kit配体Steel因子（SLF）对造血祖细胞的作用。这两种因子均与Pixy321（白细胞介素-3[IL-3]-粒细胞-巨噬细胞集落刺激因子融合蛋白）协同作用，诱导粒细胞-单核细胞（GM）和高增殖潜能（HPP）集落，并与Pixy321+促红细胞生成素（EPO）协同作用，诱导多能粒细胞-红系-单核细胞-巨核细胞集落。尽管SLF对红系限制性祖细胞（红系爆式集落形成单位）的集落形成有显著作用，但未观察到flt3L有此作用。向接种了CD34+细胞的经照射的长期骨髓培养物中添加flt3L可增加总细胞产量和祖细胞产量。对来自正常供体的分离的CD34+骨髓细胞进行的体外扩增研究表明，单独的flt3L可在体外支持GM和HPP祖细胞维持3至4周。向IL-1α+IL-3+IL-6+EPO的生长因子组合中添加flt3L对祖细胞扩增产生协同作用，与向IL-1α+IL-3+IL-6+EPO中添加SLF所观察到的协同作用相当。这些数据表明flt3L在调节原始多能造血祖细胞和定向造血祖细胞中发挥作用。
