Migliaccio G, Migliaccio A R, Kaushansky K, Adamson J W
Department of Medicine, University of Washington, Seattle 98195.
Exp Hematol. 1989 Feb;17(2):110-5.
We have examined the effect of interleukin 3 (IL-3), granulocyte-macrophage (GM)-, granulocyte (G)-, and macrophage (M)-colony-stimulating factors (CSFs) on the induction of GM colonies from highly enriched murine hematopoietic progenitor cells under serum-deprived conditions. Each growth factor was tested alone or in combination with suboptimal concentrations of the others. The effect of each CSF on GM colony growth in fetal bovine serum (FBS)-supplemented cultures of unfractionated marrow cells is reported for comparison. GM-CSF induced GM colony growth in serum-deprived cultures of purified progenitor cells to the same extent as in FBS-supplemented cultures of unfractionated marrow cells. In contrast, IL-3 was only one-tenth as active in promoting the growth of enriched progenitor cells under serum-deprived conditions when compared with its effect on colony growth from unfractionated marrow. M-CSF and G-CSF were almost completely ineffective in both cases. G-CSF induction of GM colony growth from purified progenitor cells was restored by addition of suboptimal concentrations of IL-3 or GM-CSF, suggesting that either IL-3 or GM-CSF is required to observe the effect of G-CSF. Addition of G-CSF to GM-CSF-stimulated cultures did not increase the maximal number of colonies detected, indicating that these two growth factors may act on the same subset of progenitor cells. Addition of GM-CSF or IL-3 to IL-3- or GM-CSF-stimulated cultures, respectively, increased by 40% the maximal number of colonies detected, suggesting that these two factors act on at least partially separate subsets of GM progenitors. These data parallel the recent observations on the control of human GM colony formation under FBS-deprived conditions and support a model for the control of myeloid differentiation that requires the interplay of different growth factors.
我们研究了白细胞介素3（IL-3）、粒细胞-巨噬细胞（GM）、粒细胞（G）和巨噬细胞（M）集落刺激因子（CSF）对血清饥饿条件下高度富集的小鼠造血祖细胞诱导GM集落形成的影响。每种生长因子单独进行测试，或与其他因子的次优浓度联合测试。为作比较，报告了每种CSF对未分级骨髓细胞的胎牛血清（FBS）补充培养物中GM集落生长的影响。GM-CSF在纯化祖细胞的血清饥饿培养物中诱导GM集落生长的程度，与在未分级骨髓细胞的FBS补充培养物中相同。相比之下，与IL-3对未分级骨髓集落生长的影响相比，在血清饥饿条件下，IL-3促进富集祖细胞生长的活性仅为其十分之一。在这两种情况下，M-CSF和G-CSF几乎完全无效。通过添加次优浓度的IL-3或GM-CSF可恢复G-CSF对纯化祖细胞GM集落生长的诱导作用，这表明观察G-CSF的作用需要IL-3或GM-CSF。向GM-CSF刺激的培养物中添加G-CSF不会增加检测到的集落最大数量，表明这两种生长因子可能作用于同一祖细胞亚群。分别向IL-3或GM-CSF刺激的培养物中添加GM-CSF或IL-3，可使检测到的集落最大数量增加40%，表明这两种因子至少部分作用于GM祖细胞不同的亚群。这些数据与最近关于FBS饥饿条件下人类GM集落形成调控的观察结果一致，并支持一种需要不同生长因子相互作用的髓系分化调控模型。
