Völkers B, Ganser A, Greher J, Stella C C, Hoelzer D
Abteilung für Hämatologie, Zentrum der Inneren Medizin, Universität Frankfurt.
Onkologie. 1989 Jun;12(3):109-15. doi: 10.1159/000216616.
The effect of human recombinant tumor necrosis factor (rhTNF-alpha) on the in vitro colony growth of normal hematopoietic progenitor cells was investigated. In a clonal colony-assay a dose-dependent inhibition of erythroid BFU-E, granulocyte/monocyte CFU-GM and megakaryocyte CFU-Mk was demonstrated. CFU-Mk were completely inhibited by low doses of TNF-alpha (3 U-300 U/ml). 50% inhibition occurred at 10 U/ml of TNF for CFU-Mk, 100% inhibition at 300 U/ml of TNF. 50% inhibition occurred at 233 U/ml of TNF for CFU-GM, and 100% inhibition for CFU-GM was not observed. For inhibition of BFU-E higher doses of TNF-alpha were necessary (100 U-1,000 U/ml). The growth inhibitory effect could selectively be abolished by antibodies against TNF-alpha. Removal of adherent cells and T-lymphocytes from the bone marrow cells had no significant influence of the suppressive effect of TNF-alpha. The inhibitory effect of TNF-alpha is due to a direct action on hematopoietic progenitor cells and not mediated by accessory cells.
研究了人重组肿瘤坏死因子（rhTNF-α）对正常造血祖细胞体外集落生长的影响。在克隆集落测定中，证实了对红系爆式集落形成单位（BFU-E）、粒细胞/单核细胞集落形成单位（CFU-GM）和巨核细胞集落形成单位（CFU-Mk）有剂量依赖性抑制作用。低剂量的TNF-α（3 U - 300 U/ml）可完全抑制CFU-Mk。CFU-Mk在10 U/ml的TNF时出现50%抑制，在300 U/ml的TNF时出现100%抑制。CFU-GM在233 U/ml的TNF时出现50%抑制，未观察到CFU-GM的100%抑制。对于BFU-E的抑制需要更高剂量的TNF-α（100 U - 1000 U/ml）。抗TNF-α抗体可选择性地消除生长抑制作用。从骨髓细胞中去除贴壁细胞和T淋巴细胞对TNF-α的抑制作用没有显著影响。TNF-α的抑制作用是由于对造血祖细胞的直接作用，而非由辅助细胞介导。
