DIFFERENTIATION OF GRANULOCYTES AND MACROPHAGES

粒细胞和巨噬细胞的分化

• 批准号: 3165857
• 负责人: DONALD METCALF
• 金额: $ 6.35万
• 依托单位: WALTER AND ELIZA HALL INST MEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-03-01 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3165857
• 关键词: cell differentiation; cell growth regulation; colony stimulating factor; eukaryote; gene expression; genetic library; granulocyte; hematopoietic stem cells; histochemistry /cytochemistry; macrophage; molecular cloning; monoclonal antibody; myelogenous leukemia; phosphorylation; radioassay

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)

本项目的目标是表征的分子控制 骨髓性白血病细胞，首先建立的性质， 控制细胞分裂的糖蛋白（集落刺激因子，CSF） 正常粒细胞和巨噬细胞的分化， 确定CSF对白血病细胞的作用。 我们建立 四种糖蛋白相互作用来控制正常小鼠的粒细胞， 巨噬细胞：GM-CSF、M-CSF、G-CSF和MultiCSF（IL-3）。 这四个人都 被少量纯化至均匀。 已经克隆了cDNA， 细菌表达的GM-CSF和Multi-CSF及其重组材料 具有与天然分子相似的体外和体内性质。 我们 已经确定G-CSF可以通过以下方式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 表明白血病细胞上的受体数量与 正常的GM前体细胞 分化无反应性白血病细胞 已经显示缺乏G-CSF的膜受体。这些研究报告将 使用放射性标记的GM-CSF进行扩展， 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，并且正在尝试克隆cDNA 对于G-CSF，这是大规模生产G-CSF的第一步。 （百万）