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白细胞介素-3、粒细胞集落刺激因子和粒细胞-巨噬细胞集落刺激因子对高度富集的人造血祖细胞的作用:粒细胞-巨噬细胞集落刺激因子加粒细胞集落刺激因子的协同相互作用

Action of interleukin-3, G-CSF, and GM-CSF on highly enriched human hematopoietic progenitor cells: synergistic interaction of GM-CSF plus G-CSF.

作者信息

McNiece I, Andrews R, Stewart M, Clark S, Boone T, Quesenberry P

机构信息

Department of Internal Medicine, University of Virginia, Charlottesville.

出版信息

Blood. 1989 Jul;74(1):110-4.

PMID:2473792
Abstract

Purified preparations of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and interleukin 3 (IL-3 or multi-CSF) alone and in combination, have been compared for their stimulatory effects on human granulocyte-macrophage colony forming cells (GM-CFC). In cultures of unseparated normal human bone marrow, the combinations of G-CSF plus IL-3 and GM-CSF plus IL-3 stimulated additive numbers of GM colonies, while GM-CSF plus G-CSF stimulated greater than additive numbers of GM colonies, compared with the sum of the colony formation obtained with each factor alone. Cultures of unseparated bone marrow, harvested from patients four to six days after administration of 5-fluorouracil (5-FU), resulted in additive GM colony formation with GM-CSF plus G-CSF, GM-CSF plus IL-3, and G-CSF plus IL-3. In order to address the possibility of secondary factor involvement in the synergistic interaction of GM-CSF and G-CSF, CD33+/CD34+ colony forming cells were separated from normal and post FU marrow by two color fluorescence activated cell sorting. In cultures of CD33+/CD34+ cells the combination of GM-CSF plus G-CSF stimulated a synergistic increase in GM colonies while GM-CSF plus IL-3 stimulated additive numbers of colonies. These results suggest that GM-CSF, G-CSF, and IL-3 stimulate distinct populations of GM-CFC. Furthermore GM-CSF and G-CSF interact synergistically and this action is a direct effect on progenitor cells not stimulated by GM-CSF or G-CSF alone.

摘要

已对重组人粒细胞巨噬细胞集落刺激因子(GM-CSF)、粒细胞集落刺激因子(G-CSF)和白细胞介素3(IL-3或多集落刺激因子)单独及联合使用的纯化制剂对人粒细胞巨噬细胞集落形成细胞(GM-CFC)的刺激作用进行了比较。在未分离的正常人骨髓培养物中,与单独使用每种因子所获得的集落形成总和相比,G-CSF加IL-3以及GM-CSF加IL-3的组合刺激产生了相加数量的GM集落,而GM-CSF加G-CSF刺激产生的GM集落数量大于相加数量。对接受5-氟尿嘧啶(5-FU)给药后四至六天的患者采集的未分离骨髓进行培养,结果显示GM-CSF加G-CSF、GM-CSF加IL-3以及G-CSF加IL-3产生了相加的GM集落形成。为了探讨在GM-CSF和G-CSF的协同相互作用中是否有次级因子参与,通过双色荧光激活细胞分选从正常和FU后骨髓中分离出CD33+/CD34+集落形成细胞。在CD33+/CD34+细胞培养物中,GM-CSF加G-CSF的组合刺激GM集落协同增加,而GM-CSF加IL-3刺激产生相加数量的集落。这些结果表明,GM-CSF、G-CSF和IL-3刺激不同群体的GM-CFC。此外,GM-CSF和G-CSF协同相互作用,并且这种作用是对单独不受GM-CSF或G-CSF刺激的祖细胞的直接作用。

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