干扰素γ介导噬血细胞综合征血细胞减少的机制研究

Mechanism of interferon gamma mediated hemophagocytic syndrome blood cell reduction

目的探讨噬血细胞综合征患者与正常人骨髓CD34+细胞质量的差异情况,研究干扰素γ对骨髓分化的影响和特点,并观察提高集落刺激因子对干扰素γ抑制骨髓作用的对抗情况。方法采用免疫磁珠法分离纯化骨髓CD34+造血干细胞。在体外扩增培养中,以干细胞因子(stem cell factor,SCF)和白介素-3(interleukin-3,IL-3)、粒细胞-巨噬细胞集落刺激因子(granulocyte macrophage-colony stimulating factor,GM-CSF)、粒细胞集落刺激因子(granulocyte-colony stimulating factor,G-CSF)、促红细胞生成素(erythropoietin,EPO)集落刺激因子组合对骨髓干细胞诱导分化,以集落形成单位(colony forming units,CFU)的形成数来评价骨髓分化情况,在体系中加入不同浓度梯度的干扰素γ,观察骨髓集落形成情况。在干扰素γ抑制骨髓的最低浓度下增加集落刺激因子浓度,观察骨髓生长情况。结果患者骨髓CD34+细胞质量与正常人相比差异无统计学意义(P>0.05);不同浓度的干扰素γ对骨髓的抑制程度不同,当干扰素γ浓度提高到10 ng/mL以上时,实验组的集落数目相比于未添加干扰素γ的对照组,差异有统计学意义(P<0.05);增加培养体系中集落刺激因子浓度可对抗因干扰素γ使骨髓出现的抑制作用情况。结论噬血细胞综合征患者与正常人骨髓质量不存在差异,干扰素γ可以对骨髓生长起抑制作用,提高集落刺激因子浓度可以对抗干扰素γ产生的抑制作用。

Objective To explore whether there are differences between hemophagocytic syndrome patients and normal human bone marrow CD34＋cells＇ quality,study the effect and characteristics of interferon gamma differentiation to the bone marrow,and observe whether improved colony stimulating factor can restrain the inhibition of interferon gamma on bone marrow. Methods Separation and purification of bone marrow CD34＋hematopoietic stem cells were performed by immunomagnetic beads method. SCF,IL 3,GM-CSF,GCSF,EPO colony stimulating factor on differentiation of bone marrow stem cells,the colony forming units（ CFU） to evaluate the formation of bone marrow differentiation. Added different concentration gradient of interferon gamma in the system,observation the bone marrow colony formation the situation. Increase in the minimum concentrations interferon gamma inhibition of bone marrow in colony stimulating factor concentration to observe the bone marrow growth situation. Results This study demonstrated no difference in bone marrow CD34＋cells compared with normal quality（ P 0. 05）. The degree of inhibition of interferon gamma in different concentration on bone marrow is different,when interferon gamma concentration increased to more than 10 ng /mL,the experimental group colony number difference compared to the control group without the addition of interferon gamma（ P 0. 05）. To increase the training system of colony stimulating factors concentration can be made against the bone marrow suppression of interferon gamma. Conclusion There was no significant difference in bone marrow＇s quality between HPS patients and normal control. Interferon gamma may inhibit bone marrow＇s growth.Increased colony stimulating factor concentration may act against interferon gamma production.