COMPARATIVE-STUDIES OF THE ERYTHROID-POTENTIATING EFFECTS OF BIOSYNTHETIC HUMAN INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II

COMPARATIVE-STUDIES OF THE ERYTHROID-POTENTIATING EFFECTS OF BIOSYNTHETIC HUMAN INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II
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DOI:
10.1210/jc.74.2.447
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发表时间:
1992-02-01
影响因子:
5.8
通讯作者:
SKOTTNER, A
SKOTTNER, A
中科院分区:
医学2区
文献类型:
--
作者:
MERCHAV, S;SILVIANDRACHSLER, I;SKOTTNER, A

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生物合成的人胰岛素样生长因子- i (IGF-I)和IGF-II在人骨髓红细胞祖细胞无血清培养中的促红细胞增强作用进行了评价和比较。IGF-I和IGF-II以相似的剂量依赖性促进相对成熟(CFU-E)和原始(BFU-E)红细胞祖细胞的体外生长。两种肽浓度在0.2 ~ 0.6 ng/mL时,红细胞集落计数显著升高,2 ~ 6 ng/mL时,CFU-E和BFU-E数量增加最多。在辅助细胞缺失的骨髓细胞或高度富集的造血祖细胞培养物中,两种多肽对红系祖细胞生长的类似增强作用也被检测到。IGF-I和IGF-II在限制浓度和饱和浓度的重组人促红细胞生成素或粒细胞巨噬细胞集落刺激因子下均能促进红细胞祖细胞的生长,但不改变CFU-E和BFU-E对各自造血调节因子的敏感性。针对IGF-I膜受体的单克隆抗体完全消除了IGF-I和IGF-II的促红细胞增强作用。因此,IGF-I和IGF- ii似乎通过涉及I型IGF受体的直接机制对人骨髓红细胞祖细胞发挥作用。
The erythroid-potentiating effects of biosynthetic human insulin-like growth factor-I (IGF-I) and IGF-II were evaluated and compared in serum-free cultures of human marrow erythroid progenitors. IGF-I and IGF-II enhanced the in vitro growth of relatively mature (CFU-E) and primitive (BFU-E) erythroid progenitors at similar dose-dependent magnitudes. Significant elevations in erythroid colony counts were detected at 0.2-0.6 ng/mL of both peptides, with a maximal increase in CFU-E and BFU-E numbers detected at 2-6 ng/mL. Similar enhancement of erythroid progenitor cell growth by both peptides was also detected in cultures of marrow cells that had been depleted of accessory cells or in cultures of highly enriched hemopoietic progenitors. IGF-I and IGF-II enhanced erythroid progenitor cell growth at both limiting and saturating concentrations of recombinant human erythropoetin or granulocytemacrophage colony-stimulating factor, but did not alter the sensitivity of CFU-E and BFU-E to their respective hemopoietic regulators. The erythroid-potentiating effects of IGF-I and IGF-II were completely abrogated by monoclonal antibodies directed against IGF-I membrane receptors. IGF-I and IGF-II thus appear to exert their effects on human marrow erythroid progenitors via a direct mechanism involving the type I IGF receptor.