Schwartz G N, Liao F, Gress R E, Farber J M
Department of Experimental Transplantation and Immunology, National Cancer Institute, Bethesda, MD 20892, USA.
J Immunol. 1997 Jul 15;159(2):895-904.
Studies in this report investigated potential hemopoietic suppressive effects of human monokine induced by IFN-gamma (HuMig), a CXC chemokine that is chemotactic for activated lymphocytes. rHuMig was purified from Trichoplusia ni cells after infection with a recombinant baculovirus. The recombinant protein was added to liquid cultures of CD34+ human marrow cells stimulated with IL-3 alone or with both IL-3 and either insulin-like growth factor II (IGF-II) or stem cell growth factor (SCF). The number of committed progenitors, colony-forming units for granulocytes and macrophages (CFU-GM), and primitive progenitors, long term culture-initiating cells (LTC-IC) derived from liquid cultures of CD34+ cells, was determined. rHuMig abrogated the IGF-II-dependent enhancement of CFU-GM and long term culture-initiating cell numbers. Additional studies demonstrated that in liquid cultures of CD34+ cells both rHuMig and IFN-inducible protein-10, another CXC chemokine that is related to HuMig, inhibited the production or expansion of CFU-GM. For a subset of marrows, rHuMig also abrogated SCF enhancement of CFU-GM numbers in cultures of CD34+ cells stimulated with both IL-3 and SCF. These studies are the first to demonstrate that rHuMig can act as a negative regulator of in vitro hemopoiesis, that both rHuMig and IP-10 can suppress an increase in the number of committed progenitors from CD34+ cells, and that chemokines can abrogate hemopoietic stimulatory effects of IGF-II.
本报告中的研究调查了γ干扰素诱导的人单核因子（HuMig，一种对活化淋巴细胞具有趋化作用的CXC趋化因子）潜在的造血抑制作用。重组人HuMig（rHuMig）是在用重组杆状病毒感染的粉纹夜蛾细胞中纯化得到的。将该重组蛋白添加到单独用白细胞介素-3（IL-3）刺激或用IL-3与胰岛素样生长因子II（IGF-II）或干细胞生长因子（SCF）共同刺激的CD34⁺人骨髓细胞的液体培养物中。测定了来自CD34⁺细胞液体培养物的定向祖细胞、粒细胞和巨噬细胞集落形成单位（CFU-GM）以及原始祖细胞、长期培养起始细胞（LTC-IC）的数量。rHuMig消除了IGF-II对CFU-GM和长期培养起始细胞数量的依赖性增强作用。进一步的研究表明，在CD34⁺细胞的液体培养物中，rHuMig和干扰素诱导蛋白-10（与HuMig相关的另一种CXC趋化因子）均抑制CFU-GM的产生或扩增。对于一部分骨髓，rHuMig还消除了在同时用IL-3和SCF刺激的CD34⁺细胞培养物中SCF对CFU-GM数量的增强作用。这些研究首次证明rHuMig可作为体外造血的负调节因子，rHuMig和IP-10均可抑制CD34⁺细胞定向祖细胞数量的增加，并且趋化因子可消除IGF-II的造血刺激作用。
