DIFFERENTIATION OF GRANULOCYTES AND MACROPHAGES

粒细胞和巨噬细胞的分化

• 批准号: 3165859
• 负责人: DONALD METCALF
• 金额: $ 7.2万
• 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 1990-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3165859
• 关键词: cell differentiation; cell growth regulation; colony stimulating factor; eukaryote; gene expression; genetic library; granulocyte; hematopoietic stem cells; histochemistry /cytochemistry; laboratory mouse; macrophage; molecular cloning; monoclonal antibody; myelogenous leukemia; phosphorylation; protein biosynthesis; protein sequence; radioassay; receptor

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)

这个项目的目的是表征分子控制