Piacibello W, Sanavio F, Severino A, Morelli S, Vaira A M, Stacchini A, Aglietta M
Department of Biomedical Sciences and Human Oncology, Clinica Medica I, Torino, Italy.
Cancer Res. 1990 Aug 15;50(16):5065-71.
The effect of recombinant human tumor necrosis factor alpha (TNF-alpha) on normal and chronic myeloid leukemia granulocyte-macrophage progenitors (CFU-GM) growing in semisolid agar cultures in the presence of recombinant granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor was studied. Granulocyte-macrophage colony-stimulating factor-dependent growth of normal and chronic myeloid leukemia bone marrow CFU-GM was greatly enhanced by TNF-alpha at doses of 0.1 to 100 units/ml. Growth enhancement included neutrophil, eosinophil, and monocyte-macrophage colonies and clusters at 7 and 14 days of culture. Since similar results were achieved with highly enriched progenitor cell populations, devoid of accessory cells, an indirect effect on CFU-GM growth through the release by accessory cells of other cytokines upon TNF-alpha stimulation was thus ruled out. By contrast, the same doses of TNF-alpha inhibited the growth of normal CFU-GM in granulocyte colony-stimulating factor-dependent cultures. Taken together, our findings indicate that the final effect of TNF-alpha on normal bone marrow granulocyte-macrophage progenitor growth is dependent on the specific growth factor interacting with it, and that both normal and chronic myeloid leukemia CFU-GM are equally responsive to the combined effects of TNF-alpha and a given colony-stimulating factor.
研究了重组人肿瘤坏死因子α（TNF-α）对在重组粒细胞集落刺激因子和粒细胞-巨噬细胞集落刺激因子存在下于半固体琼脂培养物中生长的正常和慢性髓性白血病粒细胞-巨噬细胞祖细胞（CFU-GM）的影响。在0.1至100单位/毫升的剂量下，TNF-α极大地增强了正常和慢性髓性白血病骨髓CFU-GM依赖粒细胞-巨噬细胞集落刺激因子的生长。生长增强包括培养7天和14天时的中性粒细胞、嗜酸性粒细胞以及单核细胞-巨噬细胞集落和集簇。由于在高度富集的、不含辅助细胞的祖细胞群体中也获得了类似结果，因此排除了TNF-α刺激后辅助细胞释放其他细胞因子对CFU-GM生长产生的间接影响。相比之下，相同剂量的TNF-α在依赖粒细胞集落刺激因子的培养物中抑制正常CFU-GM的生长。综上所述，我们的研究结果表明，TNF-α对正常骨髓粒细胞-巨噬细胞祖细胞生长的最终影响取决于与其相互作用的特定生长因子，并且正常和慢性髓性白血病CFU-GM对TNF-α和特定集落刺激因子的联合作用同样敏感。
