Functional and biochemical characterization of a novel human macrophage-derived negative regulator of haematopoiesis.
Functional and biochemical characterization of a novel human macrophage-derived negative regulator of haematopoiesis.
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新型人巨噬细胞衍生的造血负调节因子的功能和生化特征。
DOI：
10.1006/cyto.1999.0507
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Yu,J
中科院分区：
文献类型：
--
作者：
Dialynas,DP;Shao,LE;Hinojosa,AG;Yu,J
据信，造血受来自骨髓微环境（包括巨噬细胞）的正信号和负信号调节。介导负调控的蛋白质的身份和作用机制是一个积极的研究领域。我们在这里报告的早期造血祖细胞，指定NRH（负调节造血），从最近建立的人巨噬细胞系2MAC分离的一种新的抑制剂的识别和初步表征。NRH抑制的机制似乎涉及早期祖细胞循环的显著减少。NRH活性被证明是可逆的，并且对应于分子量约为20000道尔顿（约20kDa）的酸性肝素结合糖蛋白。通过利用凝集素特异性，疏水相互作用，和肝素的亲和力，我们已经开发了一种程序，用于快速分离高度纯化的NRH从2MAC条件培养基。通过一些功能和生化标准，NRH似乎代表了一种新的巨噬细胞衍生的造血负调节因子，其可能在某些临床环境中作为原始造血细胞的化学保护剂具有未来的应用。
It is believed that haematopoiesis is regulated by both positive and negative signals derived from the marrow microenvironment, which includes macrophages. The identity and mechanism of action of the proteins mediating negative regulation is an area of active investigation. We report here the identification and initial characterization of a novel suppressor of early haematopoietic progenitors, designated NRH (for Negative Regulator of Haematopoiesis), isolated from the recently established human macrophage line 2MAC. The mechanism of NRH suppression appears to involve a marked decrease in the cycling of early progenitor cells. NRH activity was shown to be reversible and to correspond to an acidic, heparin-binding glycoprotein with a molecular weight of approximately 20000 daltons (∼20kDa). By exploiting lectin specificity, hydrophobic interaction, and heparin affinity, we have developed a procedure for the rapid isolation of highly purified NRH from 2MAC-conditioned medium. By a number of functional and biochemical criteria, NRH appears to represent a novel macrophage-derived negative regulator of haematopoiesis which may have future application in certain clinical settings as a chemoprotectant of primitive haematopoietic cells.