Stem cell factor can overcome inhibition of highly purified human burst-forming units-erythroid by interferon gamma.
Stem cell factor can overcome inhibition of highly purified human burst-forming units-erythroid by interferon gamma.
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干细胞因子可以克服干扰素γ对高度纯化的人类爆发形成单位-红细胞的抑制。
DOI：
10.1002/jcp.1041650213
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发表时间：
1995
影响因子：
5.6
通讯作者：
Price,JO
中科院分区：
文献类型：
--
作者：
Dai,CH;Krantz,SB;Kollar,K;Price,JO
使用高度纯化的人血爆发形成单位红细胞 (BFU-E) 来研究干扰素 γ (IFNγ) 的作用。 IFNγ 以剂量依赖性方式抑制第 3 天至第 6 天成熟 BFU-E 的红系集落形成、细胞增殖和分化。原始 BFU-E（第 1 天和第 2 天细胞）和后来的第 7 天细胞受影响较小。 IFNγ剂量反应实验表明，红细胞集落的数量和大小在 500 U/ml 浓度下减少，在 1,000 U/ml 浓度下抑制更完全。通过与 IFNγ 孵育 72 小时，首先注意到第 4 天至第 6 天红系祖细胞的抑制，并且随着进一步孵育，靶细胞生长和分化继续减少。 IFNγ还诱导成红细胞凋亡，这通过核浓缩和碎裂以及原位末端标记的流式细胞术得到证实。由于第 3 天至第 6 天的细胞需要干细胞因子 (SCF) 在无血清培养中发育，因此研究了 IFNγ 抑制与该生长因子的关系。尽管集落大小并未完全重建，但 SCF 逆转了 IFNγ 导致的红系集落数量减少。相比之下，白细胞介素-3 没有能力克服 IFNγ 的抑制作用。由于某些慢性疾病贫血中 IFNγ 血液水平升高，IFNγ 可能对这种贫血有促进作用，并且 SCF 加 EP 可能会更好地克服其抑制作用。然而，目前尚不清楚这些生长因子克服 IFNγ 抑制的机制，反之亦然。 © 1995 Wiley-Liss, Inc.
Highly purified human blood burst‐forming units‐erythroid (BFU‐E) were used to study the effects of interferon γ (IFNγ). IFNγ inhibited erythroid colony formation, cell proliferation, and differentiation of day 3 to day 6 mature BFU‐E in a dose‐dependent manner. The primitive BFU‐E (day 1 and day 2 cells) and later day 7 cells were less affected. IFNγ dose‐response experiments demonstrated that the number and size of erythroid colonies were reduced at a concentration of 500 U/ml with more complete inhibition at 1,000 U/ml. Inhibition of day 4 to day 6 erythroid progenitors was first noted by 72 h of incubation with IFNγ, and target cell growth and differentiation continued to decrease with further incubation. IFNγ also induced erythroblast apoptosis which was demonstrated by both nuclear condensation and fragmentation plus flow cytometry with in situ end‐labelling. Because day 3 to day 6 cells need stem cell factor (SCF) for development in serum‐free culture, the relationship of IFNγ inhibition to this growth factor was investigated. The reduction in the number of erythroid colonies by IFNγ was reversed by SCF although the colony size was not completely re‐established. In contrast, interleukin‐3 did not have the capacity to overcome the inhibitory effects of IFNγ. Since IFNγ blood levels are elevated in some anemias of chronic disease, IFNγ may have a role in promoting this anemia and its inhibitory effect might be better overcome by SCF plus EP. However, the mechanism by which these growth factors overcome the inhibition of IFNγ, or vice versa, is unknown at the present time. © 1995 Wiley‐Liss, Inc.