INTERLEUKIN-6 ENHANCEMENT OF INTERLEUKIN-3-DEPENDENT PROLIFERATION OF MULTIPOTENTIAL HEMATOPOIETIC PROGENITORS

INTERLEUKIN-6 ENHANCEMENT OF INTERLEUKIN-3-DEPENDENT PROLIFERATION OF MULTIPOTENTIAL HEMATOPOIETIC PROGENITORS
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DOI:
10.1073/pnas.84.24.9035
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发表时间:
1987-12-01
影响因子:
11.1
通讯作者:
OGAWA, M
OGAWA, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
IKEBUCHI, K;WONG, GG;OGAWA, M

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白介素6(IL-6,又称B细胞刺激因子2/干扰素β2)可促进粒细胞/巨噬细胞祖细胞的增殖,并间接支持正常小鼠脾细胞培养的多系和原始细胞集落形成。我们在此报告,IL-3和IL-6在支持小鼠多潜能祖细胞在培养中的增殖方面具有协同作用。小鼠脾细胞注射5-氟尿嘧啶(150 mg/kg)4天后,加入两种淋巴因子的小鼠脾细胞集落形成时间明显短于两种因子中任何一种。对培养中单个原始细胞克隆的连续观察(图谱)显示,在IL-3存在下,原始细胞克隆在随机时间间隔后出现。单独在IL-6中出现的平均时间有所延迟,并且在包含两种因素的培养中,与在单个淋巴因子存在下生长的培养物相比,多系原始细胞集落的出现明显加快。在5-氟尿嘧啶后第2天的骨髓细胞培养中,IL-6不支持集落形成;IL-3单独支持少数粒/巨噬细胞集落的形成,但多种因素的组合协同作用产生了多系集落和各种其他类型的集落。在这个系统中,IL-1α。与IL-3也有协同作用,但作用较小,未见多系集落形成。综上所述,这些结果表明,IL-3和IL-6协同作用支持造血祖细胞的增殖,至少部分效果是由于单个干细胞GO周期的缩短。
Interleukin-6 (IL-6, also known as B-cell stimulatory factor 2/interferon .beta.2) was previously shown to support the proliferation of granulocyte/macrophage progenitors and indirectly support the formation of multilineage and blast cell colonies in cultures of spleen cells from normal mice. We report here that IL-3 and IL-6 act synergistically in support of the proliferation of murine multipotential progenitors in culture. The time course of total colony formation by spleen cells isolated from mice 4 days after injection of 5-flourouracil (150 mg/kg) was significantly shortened in cultures containing both lymphokines relative to cultures supported by either of the two factors. Serial observations (mapping) of individual blast cell colonies in culture revealed that blast cell colonies emerged after random time intervals in the presence of IL-3. The average time of appearance in IL-6 alone was somewhat delayed, and in cultures containing both factors the appearance of multilineage blast cell colonies was significantly hastened relative to cultures grown in the presence of the individual lymphokines. In cultures of day-2 post-5-flourouracil bone marrow cells, IL-6 failed to support colony formation; IL-3 alone supported the formation of a few granulocyte/macrophage colonies, but the combination of factors acted synergistically to yield multilineage and a variety of other types of colonies. In this system, IL-1.alpha. also acted synergistically with IL-3, but the effect was smaller, and no multilineage colonies were seen. Together these results indicate that IL-3 and IL-6 act synergistically to support the proliferation of hemopoietic progenitors and that at least part of the effect results from a decrease in the Go period of the individual stem cells.