Metcalf D, Hilton D J, Nicola N A
Cancer Research Unit, Walter and Eliza Hall Institute, Royal Melbourne Hospital, Victoria, Australia.
Leukemia. 1988 Apr;2(4):216-21.
The in vitro actions of leukemia inhibitory factor (LIF) purified from Krebs tumor conditioned medium, were analyzed on murine leukemic M1 and WEHI-3B D+ cells and on normal hemopoietic progenitor cells. LIF has no observable effects on WEHI-3B D+ cells but rapidly induced macrophage differentiation and loss of clonogenicity in M1 cells, resulting in the formation of abortive clones or differentiating colonies of reduced size and number. These effects were observable within one to two cell divisions in the presence of LIF and were irreversible. Addition of macrophage-colony-stimulating factor (CSF) but not granulocyte/macrophage-CSF, granulocyte-CSF, or multi-CSF reduced the LIF-induced suppression of colony numbers and size. G-CSF had a slower differentiation-inducing action on M1 cells than LIF but potentiated the differentiation-inducing effects of low concentrations of LIF. LIF had no colony-stimulating activity for normal granulocyte-macrophage progenitor cells and did not alter their quantitative responsiveness to CSF. However, culture of normal progenitor cells in the presence of LIF, but initial absence of CSF, reduced the survival of these cells. The differing actions of LIF and G-CSF on M1 leukemic cells suggest the existence of distinct mechanisms for inducing macrophage differentiation in these leukemic cells.
对从克雷布斯肿瘤条件培养基中纯化得到的白血病抑制因子（LIF），在小鼠白血病M1细胞和WEHI-3B D+细胞以及正常造血祖细胞上的体外作用进行了分析。LIF对WEHI-3B D+细胞没有可观察到的作用，但能迅速诱导M1细胞发生巨噬细胞分化并丧失克隆形成能力，导致形成流产克隆或大小和数量减少的分化集落。在有LIF存在的情况下，这些作用在一到两个细胞分裂内即可观察到，并且是不可逆的。添加巨噬细胞集落刺激因子（CSF）而非粒细胞/巨噬细胞-CSF、粒细胞-CSF或多能CSF可减少LIF诱导的集落数量和大小的抑制。粒细胞集落刺激因子（G-CSF）对M1细胞的分化诱导作用比LIF慢，但能增强低浓度LIF的分化诱导作用。LIF对正常粒细胞-巨噬细胞祖细胞没有集落刺激活性，也不改变它们对CSF的定量反应性。然而，在有LIF但最初没有CSF的情况下培养正常祖细胞，会降低这些细胞的存活率。LIF和G-CSF对M1白血病细胞的不同作用表明，在这些白血病细胞中存在诱导巨噬细胞分化的不同机制。
