HEMOPOIETIC STEM CELL DIFFERENTIATION TO MACROPHAGES

本项目的总体目标是研究 多能造血干细胞产生巨噬细胞以表征 参与这个过程的生长因子。三个因素影响着 这条途径已经被研究过了。 它们是殖民地刺激因子-1 （CSF-1）、促红细胞生成素-1和促红细胞生成素-2。 单核吞噬细胞 谱系特异性生长因子CSF-1已显示由两个 二硫键连接的14,000 Mr多肽链， 一模一样 二聚体蛋白质核心被N-连接的糖基化， 酸性“复合”型寡糖。 85%以上的 碳水化合物可以被去除而不损失生物学的，受体结合的， 或抗体结合活性。 然而，在没有 解离剂导致这些活性的丧失。 这些属性 CSF-1的表达是鼠和人形式的分子共有的。 在 与其他人的合作，前39个氨基酸的序列， 已经确定了鼠CSF-1的N-末端，以及 23个额外残基的内部序列。 存在高度 人和鼠CSF-1序列之间的同源性。 造血素 已被确定为调节生产的生长因子， 巨噬细胞祖细胞从发育早期的细胞。 促红细胞生成素-2本身对发育较晚的细胞具有活性， 对促红细胞生成素-1有反应的。 它已经从 由鼠细胞系条件化的无血清培养基， 具有红细胞爆发促进活性的因子的性质， 白细胞介素3。 促红细胞生成素-1需要CSF-1才能产生 巨噬细胞祖细胞 它已从无血清 由人细胞系调节的培养基。 两种造血素似乎都是 多谱系，而不是谱系特异性造血生长因子。 （MB）

The overall aim of this project is to investigate the mechanisms by which pluripotent hemopoietic stem cells give rise to macrophages to characterize the growth factors involved in this process. Three factors implicated in this pathway have been studied. They are the colony stimulating factor-1 (CSF-1), hemopoietin-1, and hemopoietin-2. The mononuclear phagocyte lineage specific growth factor, CSF-1, has been shown to consist of two disulfide-bonded, 14,000 Mr polypeptide chains that are possibly identical. The dimeric protein core is heavily glycosylated with N-linked oligosaccharides of the acidic "complex" type. More than 85% of the carbohydrate can be removed without loss of biological, receptor-binding, or antibody-binding activities. However, mild reduction in the absence of dissociating agents results in loss of these activities. These properties of CSF-1 are shared by both murine and human forms of the molecule. In collaboration with others, the sequence of the first 39 amino acids at the N-terminal end of murine CSF-1 has been determined, together with an internal sequence of 23 additional residues. There is a high degree of homology between the human and murine CSF-1 sequences. The hemopoietins have been identified as growth factors that regulate the production of macrophage progenitor cells from developmentally earlier cells. Hemopoietin-2 is active, by itself, on developmentally later cells than those responsive to hemopoietin-1. It has been highly purified from the serum-free medium conditioned by a murine cell line and is similar in properties to the factor posseasing erythroid burst promoting activity and to interleukin 3. Hemopoietin-1 requires CSF-1 in order to generate macrophage progenitor cells. It has been purified from the serum-free medium conditioned by a human cell line. Both hemopoietins appear to be multilineage, rather than lineage specific, hemopoietic growth factors. (MB)