Péléraux A, Eliason J F, Odartchenko N
Swiss Institute for Experimental Cancer Research, Epalinges s/Lausanne.
Biochim Biophys Acta. 1990 Nov 12;1055(2):141-50. doi: 10.1016/0167-4889(90)90114-s.
The proliferation and differentiation of hemopoietic committed progenitor cells depend on colony stimulating factors (CSF). However, isolated mouse granulocyte-macrophage progenitor cells can still undergo limited proliferation in serum-free cultures after CSF deprivation. To test whether this is due to an accumulated pool of internalized factor, we examined the binding, internalization and degradation of radiolabelled interleukin 3 (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) in various hemopoietic cells. We found 20,000 high affinity IL-3 receptors on cells of two IL-3-dependent hemopoietic cell lines, FDC-P1 and FDC-P2 (Kd = 85 and 129 pM). FDC-P1 cells, which also respond to GM-CSF, possess 600 high-affinity GM-CSF receptors (Kd = 64 pM). Cells of both lines internalize IL-3, but only FDC-P1 cells release degraded IL-3 at a rapid rate. Both cell lines have similar dose-response curves for IL-3 and survival kinetics after factor removal. All other cells tested behave like FDC-P1, suggesting that the metabolism of IL-3 by FDC-P2 is exceptional. Our study indicates that transient proliferation of committed progenitor cells in the absence of added factors is apparently not due to a stable pool of internalized CSF but merely represents an intrinsic capability of these cells.
造血定向祖细胞的增殖和分化依赖于集落刺激因子(CSF)。然而,分离的小鼠粒细胞-巨噬细胞祖细胞在去除CSF后,在无血清培养中仍能进行有限的增殖。为了测试这是否是由于内化因子的积累池所致,我们检测了放射性标记的白细胞介素3(IL-3)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)在各种造血细胞中的结合、内化和降解情况。我们在两种依赖IL-3的造血细胞系FDC-P1和FDC-P2的细胞上发现了20,000个高亲和力IL-3受体(Kd = 85和129 pM)。也对GM-CSF有反应的FDC-P1细胞拥有600个高亲和力GM-CSF受体(Kd = 64 pM)。两种细胞系的细胞都能内化IL-3,但只有FDC-P1细胞能快速释放降解的IL-3。两种细胞系对IL-3的剂量反应曲线以及去除因子后的存活动力学相似。所有其他测试细胞的行为都与FDC-P1相似,这表明FDC-P2对IL-3的代谢情况较为特殊。我们的研究表明,在没有添加因子的情况下,定向祖细胞的短暂增殖显然不是由于内化CSF的稳定池所致,而仅仅代表了这些细胞的一种内在能力。