EDR is a stress-related survival factor from stroma and other tissues acting on early haematopoietic progenitors (E-mix)

EDR is a stress-related survival factor from stroma and other tissues acting on early haematopoietic progenitors (E-mix)
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DOI:
10.1016/j.cyto.2004.03.014
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发表时间:
2004-07-21
期刊:
影响因子:
3.8
通讯作者:
Möller, W
Möller, W
中科院分区:
医学3区
文献类型:
--
作者:
Dörmer, P;Spitzer, E;Möller, W

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红细胞分化调节因子(EDR)是一种在许多组织中产生的高度保守的自分泌因子。在WEHI-3条件培养基中检测了其对人、鼠红细胞白血病细胞系的诱导血红蛋白合成活性。详细分析了EDR函数。它能立即从细胞中释放出来,以应对各种应激条件,并能提高细胞存活率,特别是在低浓度范围和低细胞密度下。在高细胞密度和高EDR浓度下,观察到细胞死亡增加的相反作用。它在组织中的基本功能被认为是维持生长稳态。培养数周后,细胞对EDR供应的反应性下降。在新克隆的edr应答小鼠红细胞白血病细胞中也发现了这一点,这表明了分子适应过程。当细胞因子保持在低水平时,EDR扩增了7倍的人造血祖细胞。在半固体培养基(E-mix)中产生至少两个系的饱和水平下,祖细胞对EDR的反应是菌落数量平均增加1.87倍,呈钟形剂量-反应曲线。对于较成熟的BFU-E室,特别是在菌落数量较低的情况下,观察到反应。考虑到EDR能从辐照的基质细胞中释放出来,并能部分替代伯基特淋巴瘤细胞系BL-70中的基质细胞,EDR可作为基质应答细胞的基质存活因子。(C) 2004 Elsevier Ltd.版权所有。
The erythroid differentiation regulator (EDR) is a highly conserved autocrine factor produced in many tissues. Its haemoglobin synthesis-inducing activity for human and murine erythroleukaernia cell lines had been detected in WEHI-3 conditioned medium. EDR functions were analysed in detail. It is released from cells immediately in response to various stressful conditions and enhances cell survival particularly at a lower concentration range and low cell density. At high cell density and high EDR concentration the opposite effect of an increase in cell death was observed. Its essential function within a tissue is considered to be the maintenance of growth homeostasis.Cells kept in culture for weeks show a decreasing responsiveness to EDR supply. This was also noted in freshly cloned EDR-responsive mouse erythroleukaernia cells pointing to a molecular adaptation process. Human haematopoietic progenitors were amplified 7-fold by EDR when kept at low cytokine levels. At saturating levels progenitors giving rise to at least two lineages in semisolid medium (E-mix) respond to EDR with an average 1.87-fold increase in colony numbers and a bell-shaped dose-response curve. Of the more mature BFU-E compartment a response was observed particularly in cases with low colony numbers. Given the release from irradiated stromal cells and the ability to partly substitute for stromal cells in the Burkitt's lymphoma cell line BL-70, EDR functions as a stromal survival factor for stroma-responsive cells. (C) 2004 Elsevier Ltd. All rights reserved.