Interferon-gamma exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development.

Wang CQ; Udupa KB; Lipschitz DA

摘要

Interferon-gamma (INF-gamma) has been shown to suppress erythropoiesis and perhaps to contribute to the anemia of chronic disease. In this study we demonstrated that the concentration of INF gamma required to suppress murine burst forming unit-erythroid (BFU-E) growth was significantly less than that required to suppress colony forming unit-erythroid (CFU-E) growth. INF gamma acted at the most primitive step in erythroid progenitor cell differentiation and proliferation, as inhibition was maximal when added at the time of BFU-E culture initiation. Inhibition was progressively less if INF gamma addition was delayed after culture initiation. The effects of INF gamma on BFU-E did not require the presence of interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF alpha), or granulocyte macrophage colony stimulating factor (GM-CSF), as its effects were not neutralized by monoclonal antibodies against IL-1 alpha, TNF alpha, or GM-CSF. This applied whether INF gamma was added to culture with individual antibodies or with a combination of all three antibodies. INF gamma was not required for IL-1 alpha- or TNF alpha-induced suppression of BFU-E, as their effects were not neutralized by a monoclonal anti-INF gamma antibody. In contrast, GM-CSF-induced suppression of BFU-E was negated by the simultaneous addition of anti-INF gamma. We have previously shown that the addition of TNF alpha does not suppress BFU-E growth in cultures from marrow depleted of macrophages. Suppression did occur, however, if a small concentration of INF gamma that does not inhibit and increasing concentration of TNF alpha were added to culture, suggesting a synergistic effect between INF-gamma and TNF alpha. These observations suggest that INF gamma is a potent direct inhibitor of erythroid colony growth in vitro. It exerts its negative regulatory effect primarily on the earliest stages of erythroid progenitor cell differentiation and proliferation, as much higher doses are required to suppress late erythroid cell development. INF gamma is also involved in GM-CSF-induced inhibition of BFU-E colony growth.

机译：移行细胞(INF-gamma)已被证明抑制红细胞生成,可能做出贡献贫血的慢性疾病。我们证明了正的浓度γ需要抑制小鼠破裂形成unit-erythroid (BFU-E)显著增长不到要求压制殖民地形成unit-erythroid (CFU-E)增长。红色的行动在最原始的一步祖细胞分化和增殖,抑制时最大添加的时候BFU-E文化开始。如果正伽马抑制越来越少除了文化启动后被推迟。正的影响γBFU-E不需要interleukin-1α(il - 1α)的存在,肿瘤坏死因子-α(TNF),或粒细胞巨噬细胞集落刺激因子(gm - csf),因为它的影响没有中和单克隆抗体对il - 1α,TNFα或gm - csf。被添加到文化与个体抗体或与所有三个抗体的结合。正伽马是il - 1α-肿瘤坏死因子不是必需的alpha-induced抑制BFU-E,作为他们的效果没有中和单克隆反步兵伽马抗体。GM-CSF-induced抑制BFU-E是否定的同时添加反步兵γ。之前我们已经表明TNF的加法α不抑制BFU-E增长文化巨噬细胞从骨髓枯竭。确实发生了,然而,如果一个小的浓度正不抑制伽马和增加肿瘤坏死因子α浓度添加到文化,建议INF-gamma之间的协同效应和肿瘤坏死因子α。正伽马是一个强有力的直接抑制剂体外红细胞集落生长。主要在负监管效应最早的红细胞祖细胞阶段分化和增殖,高得多剂量必须抑制红细胞细胞的发展。GM-CSF-induced BFU-E殖民地增长的抑制。

Interferon-gamma exerts its negative regulatory effect primarily on the earliest stages of murine erythroid progenitor cell development.

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