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首页> 外文期刊>Journal of Cellular Physiology >Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death.
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Interferon-gamma and tumor necrosis factor-alpha suppress both early and late stages of hematopoiesis and induce programmed cell death.

机译：移行细胞和肿瘤坏死因子-α抑制的早期和晚期阶段造血作用和诱导细胞程序性死亡。

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摘要

Increased expression of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in bone marrow failure disorders suggests a possible pathophysiologic role of these cytokines in disease. In this study, we tested the action of TNF-alpha and IFN-gamma on phenotypically and functionally defined stages of hematopoietic development using highly purified progenitor cell populations assayed in standardized culture systems. We hypothesized that the inhibitory effects of IFN-gamma and TNF-alpha might be related to the induction of programmed cell death. In methylcellulose colony assays, IFN-gamma and TNF-alpha inhibited the growth of early hematopoietic cells, including committed CD34+CD38+ progenitor cells and phenotypically less mature CD34+CD38- cells, with 50% decreased colony formation occurring in the range of 750-1,000 U/ml of IFN-gamma and 10-15 ng/ml of TNF-alpha. More potent suppressive effects were observed in cultures supplemented with the combination of both cytokines than in cultures treated with IFN-gamma or TNF-alpha alone. When used at these concentrations, IFN-gamma and TNF-alpha inhibited growth of CD34(+)-enriched long-term culture-initiating cells by 88% and 68%, respectively. IFN-gamma and TNF-alpha triggered apoptosis of total bone marrow and CD34+ cells, recognized by the presence of a characteristic pattern of DNA degradation after low molecular weight DNA extraction, and by detection of apoptotic cells by the in situ terminal deoxynucleotidyl transferase assay. We speculate that chronic exposure of hematopoietic tissue to TNF-alpha and IFN-gamma in vivo may result in broad depletion of the stem and progenitor cell pools. Death of these cells due to apoptosis rather than transient inhibition of proliferation may be responsible for long-lasting hematologic consequences.
机译：增加干扰素γ的表达式(IFN-gamma)和肿瘤坏死因子α(tnf)骨髓衰竭失调提出了一个可能的病理生理的作用这些细胞因子在疾病。检测tnf和IFN-gamma的作用表型和功能定义的阶段使用高纯度造血发展祖细胞数量化验标准化的文化系统。这是和IFN-gamma的抑制效应tnf可能相关的感应程序性细胞死亡。化验,IFN-gamma和tnf抑制了早期造血细胞的生长,包括CD34 + CD38 +祖细胞CD34 + CD38 -细胞表型欠成熟,集落形成发生在下降50%750 - 1000 U /毫升IFN-gamma和10 - 15ng / ml的tnf。影响被观察到在文化补充与细胞因子的组合文化对待IFN-gamma或tnf一个人。IFN-gamma和tnf抑制增长CD34(+)长期culture-initiating纯度的浓缩铀细胞88%和68%,分别。tnf引发细胞凋亡的骨头骨髓CD34 +细胞,承认的的特征模式的DNA低分子量DNA后降解凋亡细胞的提取和检测原位末端转移酶试验。暴露的tnf和造血组织IFN-gamma体内可能导致广泛的损耗干细胞和祖细胞池。这些细胞由于细胞凋亡,而不是瞬态抑制增殖负责长期血液的后果。

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