Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin.
Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin.
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DOI：
10.1182/blood.v95.12.3742.012k09_3742_3749
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发表时间：
2000-06
期刊：
影响因子：
20.3
通讯作者：
I. Choi;K. Muta;A. Wickrema;S. Krantz;J. Nishimura;H. Nawata
中科院分区：
文献类型：
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作者：
I. Choi;K. Muta;A. Wickrema;S. Krantz;J. Nishimura;H. Nawata
基于干扰素-γ可能刺激造血祖细胞存活的假设，我们检测了干扰素-γ对正常人外周血成熟红系集落形成细胞(ECFC)凋亡的影响。当细胞在干扰素-γ存在的情况下培养时，即使没有促红细胞生成素(EPO)，细胞的活力也能保持至少36小时。当用流式细胞仪检测ECFCs的凋亡时，使用Annexin V，干扰素-γ降低了细胞的凋亡程度，与EPO一样。干扰素-γ还可减少ECFCs的DNA片段化。在单独加入干扰素-γ的细胞中，可检测到Bclx的表达，但在孵育36h后其表达水平逐渐下降，且低于与EPO共同孵育的水平。用流式细胞仪或荧光酶分析法检测Fas的表达和下游caspase的激活。干扰素-γ诱导细胞Fas表达，而不激活caspase8和caspase3；去EPO诱导Fas表达，caspase8和caspase3均激活。我们认为，干扰素-γ通过调节Fas和与Bclx表达相关的机制来减少凋亡，从而产生刺激成熟红系祖细胞存活的信号。(血。2000；95：3742-3749)
Based on the hypothesis that interferon gamma (IFN-gamma) may have stimulating effects on survival of hematopoietic progenitor cells, we examined the effect of IFN-gamma on apoptosis of mature erythroid colony-forming cells (ECFCs) derived from human peripheral blood obtained from normal, healthy volunteers. When the cells were cultured in the presence of IFN-gamma, even without erythropoietin (EPO), the viability of the cells was maintained for at least 36 hours. When apoptosis of ECFCs was assessed by flow cytometric analysis', using annexin V, IFN-gamma reduced the extent of apoptosis of the cells, as well as EPO. DNA fragmentation of ECFCs was also reduced by IFN-gamma. In cells cultured with IFN-gamma alone, expression of Bcl-x was detected but the level of expression decreased gradually during incubation for 36 hours, and the expression level was lower than incubation with EPO. Fas expression and activation of downstream caspases were assessed by flow cytometric analysis or fluorometric protease assay. IFN-gamma induced Fas expression of the cells without the activation of caspase8 or caspase3 during 16 hours of incubation, while deprivation of EPO induced expression of Fas and the activation of both caspase8 and caspase3. We propose that IFN-gamma produces a stimulating signal for the survival of mature erythroid progenitor cells by reducing apoptosis through a mechanism other than modulating Fas and one related to the expression of Bcl-x. (Blood. 2000;95:3742-3749)