Eliason J F, Vassalli P
Department of Cell Biology, Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
Blood Cells. 1988;14(2-3):339-54.
The addition of recombinant murine tumor necrosis factor alpha (rmTNF-alpha) to serum-free methylcellulose cultures inhibited macrophage colony formation stimulated by purified colony stimulating factor-1 (CSF-1), recombinant granulocyte-macrophage-CSF (rmGM-CSF), and recombinant interleukin 3 (rmIl-3). The concentration of rmTNF-alpha inhibiting colony formation by 50% (IC50) was between 2 and 20 ng/ml. Erythroid colony formation in cultures with erythropoietin (EPO) alone or EPO, rmIl-3, and rmGM-CSF in combination were reduced to a much lesser extent. In established long-term marrow cultures (LTMC), addition of 20 and 200 ng/ml of rmTNF-alpha resulted in release of cells from the adherent layer during the first week. Treatment of cultures with rmTNF-alpha for 4 consecutive weeks led to prolonged inhibition of cell production lasting up to 8 weeks after cessation of treatment. One day after addition of a low dose of TNF (2 ng/ml), "fat" cells were no longer observed in the adherent layer. Our results indicate that TNF inhibition of hemopoiesis occurs both at the progenitor cell and stromal cell levels.
在无血清甲基纤维素培养物中添加重组鼠肿瘤坏死因子α（rmTNF-α）可抑制由纯化的集落刺激因子-1（CSF-1）、重组粒细胞-巨噬细胞集落刺激因子（rmGM-CSF）和重组白细胞介素3（rmIl-3）刺激的巨噬细胞集落形成。抑制集落形成50%（IC50）的rmTNF-α浓度在2至20 ng/ml之间。单独使用促红细胞生成素（EPO）或EPO、rmIl-3和rmGM-CSF联合培养时，红系集落形成的减少程度要小得多。在已建立的长期骨髓培养物（LTMC）中，添加20和200 ng/ml的rmTNF-α会导致第一周内细胞从贴壁层释放。用rmTNF-α连续处理培养物4周会导致细胞生成受到长期抑制，在停止处理后可持续长达8周。添加低剂量TNF（2 ng/ml）一天后，贴壁层中不再观察到“脂肪”细胞。我们的结果表明，TNF对造血的抑制作用发生在祖细胞和基质细胞水平。
