课题基金 / 基金详情

DIFFERENTIATION OF GRANULOCYTES AND MACROPHAGES

DIFFERENTIATION OF GRANULOCYTES AND MACROPHAGES
粒细胞和巨噬细胞的分化
批准号:
3165858
负责人:
DONALD METCALF
金额:
$5.95万
依托单位国家:
美国
项目类别:
财政年份:
1978
资助国家:
美国
项目状态:
已结题
起止时间:
1978-03-01 至 1987-02-28

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项目成果

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中文摘要
翻译
这个项目的目标是描述分子控制的 通过首先建立髓系白血病细胞的特异性性质 控制细胞分裂的糖蛋白(克隆刺激因子,CSF) 和正常粒细胞和巨噬细胞的分化,然后 确定CSF对白血病细胞的作用。我们已经确立了 四种糖蛋白相互作用控制正常的小鼠粒细胞和 巨噬细胞:粒细胞集落刺激因子、巨噬细胞集落刺激因子和多粒细胞集落刺激因子(IL-3)。四个人都有 被提纯到少量的均质。已经克隆了cDNA用于 巨噬细胞集落刺激因子和多粒细胞集落刺激因子细菌表达及重组材料 在体外和体内具有与天然分子相似的性质。我们 已经证实G-CSF可以通过以下途径抑制髓系白血病细胞 加强末端分化。使用125I标记的G-CSF,我们有 研究表明,白血病细胞上的受体数量与 正常的GM前体细胞。分化反应迟钝的白血病细胞 已被证明缺乏G-CSF的膜受体。这些研究将是 利用放射性标记GM-CSF的扩展及其遗传元件的控制 将对GM-CSF进行测序和分析。氨基酸序列数据已经被 从纯化的G-CSF中获得,目前正在尝试克隆一种 对于G-CSF来说,这是迈向大规模生产G-CSF的第一步。(M)
英文摘要
The objectives of this project are to characterize the molecular control of myeloid leukemia cells by first establishing the nature of the specific glycoproteins (colony-stimulating factors, CSFs) controlling cell division and differentiation of normal granulocytes and macrophages, then determining the actions of the CSFs on leukemia cells. We have established that four glycoproteins interact to control normal mouse granulocytes and macrophages: GM-CSF, M-CSF, G-CSF, and MultiCSF (IL-3). All four have been purified to homogeneity in small amounts. cDNAs have been cloned for GM-CSF and Multi-CSF with bacterial expression and the recombinant material has similar in vitro and in vivo properties to the native molecules. We have established that G-CSF can suppress myeloid leukemic cells by enforcing terminal differentiation. Using 125I-labeled G-CSF, we have shown that receptor numbers on leukemia cells are similar to those on normal GM precursor cells. Differentiation-unresponsive leukemia cells have been shown to lack membrane receptors for G-CSF. These studies will be extended using radiolabeled GM-CSF, and the genetic elements controlling GM-CSF will be sequenced and analyzed. Amino acid sequence data has been obtained from purified G-CSF and attempts are in progress to clone a cDNA for G-CSF, a first step towards the mass production of G-CSF. (M)
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