HEMOPOIETIC STEM CELL DIFFERENTIATION TO MACROPHAGES

这个项目的总体目标是研究 多能造血干细胞分化为巨噬细胞的特性 这一过程中涉及的增长因素。牵涉到的三个因素 这条途径已经被研究过了。它们是集落刺激因子-1 (CSF-1)、造血素-1和造血素-2。单核吞噬细胞 谱系特异性生长因子，csf-1，已被证明由两个 二硫键，14,000条MR多肽链可能是 一模一样。二聚体蛋白核心与N连接的糖基化程度很高 酸性“络合物”型低聚糖。超过85%的 碳水化合物可以在不损失生物、受体结合的情况下被去除， 或抗体结合活性。然而，在没有 解离剂会导致这些活性的丧失。这些属性 小鼠和人类形式的分子都有相同的CSF-1。在……里面 与其他人合作，前39个氨基酸的序列 小鼠CSF-1的N-末端已被确定，连同一个 23个额外残基的内部序列。有很高程度的 人和小鼠CSF-1序列的同源性。促红细胞生成素 已经被确定为调节生产的生长因素 巨噬细胞前体细胞来源于发育较早的细胞。 促红细胞生成素-2本身对发育较晚的细胞具有活性 对造血素-1有反应的患者。它已经从高度提纯的 以小鼠细胞系为条件的无血清培养液，类似于 具有促进红系爆裂活性的因子的性质和 对于白介素3。促红细胞生成素-1需要脑脊液细胞集落刺激因子-1来产生 巨噬细胞前体细胞。它是从无血清的 以人类细胞系为条件的培养液。两种造血素似乎都是 多谱系，而不是谱系特定的造血生长因子。 (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)