Tarumi T, Sawada K, Sato N, Kobayashi S, Takano H, Yasukouchi T, Takashashi T, Sekiguchi S, Koike T
Department of Internal Medicine II, Hokkaido University School of Department of Internal Medicine II, Hokkaido University School of Medicine, Japan.
Exp Hematol. 1995 Nov;23(12):1310-8.
Recombinant human interferon-alpha (rIFN-alpha) inhibits erythropoiesis, in vivo and in vitro. In an attempt to clarify mechanisms related to this inhibition, effects of rIFN-alpha on highly purified human peripheral blood burst-forming units-erythroid (BFU-E) (20-60% purity) were compared with effects on erythroid progenitors in various stages of development. Day-1 and -7 cultured cells were equivalent to primitive BFU-E and colony-forming units-erythroid (CFU-E), respectively. Day-1 BFU-E supported by recombinant human erythropoietin (rEpo) and interleukin-3 (rIL-3) was inhibited by rIFN-alpha in a dose-dependent manner, and a significant inhibition occurred at 2000 U/mL rIFN-alpha. Limiting dilution analysis demonstrated that rIFN-alpha directly inhibits BFU-E rIFN-alpha inhibited the proliferative capacity or the colony expression of erythroid progenitors, with no relation to the stage of development, but inhibition of differentiation was not apparent. This evidence suggested that apoptosis of erythroid progenitors was induced by IFN-alpha. When day-7 cells were incubated with IFN-alpha in the presence of rEpo, there was an increased breakdown of total cellular DNA into DNA fragments of less than 5 kb; hence, the inhibitory effect of IFN-alpha on erythroid progenitors may mediate apoptosis.
重组人干扰素-α（rIFN-α）在体内和体外均能抑制红细胞生成。为了阐明与这种抑制相关的机制，将rIFN-α对高度纯化的人外周血红细胞爆式集落形成单位（BFU-E）（纯度为20%-60%）的作用与对不同发育阶段的红细胞祖细胞的作用进行了比较。培养1天和7天的细胞分别相当于原始BFU-E和红细胞集落形成单位（CFU-E）。由重组人促红细胞生成素（rEpo）和白细胞介素-3（rIL-3）支持的培养1天的BFU-E被rIFN-α以剂量依赖的方式抑制，在2000 U/mL rIFN-α时出现显著抑制。极限稀释分析表明，rIFN-α直接抑制BFU-E。rIFN-α抑制红细胞祖细胞的增殖能力或集落表达，与发育阶段无关，但未观察到明显的分化抑制。这一证据表明，IFN-α诱导了红细胞祖细胞的凋亡。当培养7天的细胞在rEpo存在的情况下与IFN-α一起孵育时，总细胞DNA增加降解为小于5 kb的DNA片段；因此，IFN-α对红细胞祖细胞的抑制作用可能介导了凋亡。
