Li Wei, Wang Guanjun, Cui Jiuwei, Xue Lu, Cai Lu
Department of Hematology and Oncology, First University Hospital, PR China.
Exp Hematol. 2004 Nov;32(11):1088-96. doi: 10.1016/j.exphem.2004.07.015.
The aim of this study was to investigate the stimulating effect of low-dose radiation (LDR) on bone marrow hematopoietic progenitor cell (HPC) proliferation and peripheral blood mobilization.
Mice were exposed to 25- to 100-mGy x-rays. Bone marrow and peripheral blood HPCs (BFU-E, CFU-GM, and c-kit+ cells) were measured, and GM-CSF, G-CSF, and IL-3 protein and mRNA expression were detected using ELISA, slot blot hybridization, and Northern blot methods. To functionally evaluate LDR-stimulated and -mobilized HPCs, repopulation of peripheral blood cells in lethally irradiated recipients after transplantation of LDR-treated donor HPCs was examined by WBC counts, animal survival, and colony-forming units in the recipient spleens (CFUs-S).
75-mGy x-rays induced a maximal stimulation for bone marrow HPC proliferation (CFU-GM and BFU-E formation) 48 hours postirradiation, along with a significant increase in HPC mobilization into peripheral blood 48 to 72 hours postradiation, as shown by increases in CFU-GM formation and proportion of c-kit+ cells in the peripheral mononuclear cells. 75-mGy x-rays also maximally induced increases in G-CSF and GM-CSF mRNA expression in splenocytes and levels of serum GM-CSF. To define the critical role of these hematopoietic-stimulating factors in HPC peripheral mobilization, direct administration of G-CSF at a dose of 300 microg/kg/day or 150 microg/kg/day was applied and found to significantly stimulate GM-CFU formation and increase c-kit+ cells in the peripheral mononuclear cells. More importantly, 75-mGy x-rays plus 150 microg/kg/day G-CSF (LDR/150-G-CSF) produced a similar effect to that of 300 microg/kg/day G-CSF alone. Furthermore, the capability of LDR-mobilized donor HPCs to repopulate blood cells was confirmed in lethally irradiated recipient mice by counting peripheral WBC and CFUs-S.
These results suggest that LDR induces hematopoietic hormesis, as demonstrated by HPC proliferation and peripheral mobilization, providing a potential approach to clinical application for HPC peripheral mobilization.
本研究旨在探讨低剂量辐射（LDR）对骨髓造血祖细胞（HPC）增殖及外周血动员的刺激作用。
将小鼠暴露于25至100毫戈瑞的X射线。检测骨髓和外周血中的HPC（爆式红系集落形成单位、粒-巨噬细胞集落形成单位和c-kit+细胞），并采用酶联免疫吸附测定法、斑点杂交和Northern印迹法检测粒细胞-巨噬细胞集落刺激因子（GM-CSF）、粒细胞集落刺激因子（G-CSF）和白细胞介素-3（IL-3）的蛋白及mRNA表达。为从功能上评估LDR刺激并动员的HPC，通过白细胞计数、动物存活情况及受体脾脏中的集落形成单位（CFUs-S），检测经LDR处理的供体HPC移植后，致死性照射受体外周血细胞的重建情况。
75毫戈瑞的X射线在照射后48小时对骨髓HPC增殖（CFU-GM和BFU-E形成）产生最大刺激作用，同时在照射后48至72小时，外周血中HPC动员显著增加，表现为CFU-GM形成增加以及外周单个核细胞中c-kit+细胞比例升高。75毫戈瑞的X射线还最大程度地诱导脾细胞中G-CSF和GM-CSF mRNA表达增加以及血清GM-CSF水平升高。为确定这些造血刺激因子在HPC外周动员中的关键作用，给予300微克/千克/天或150微克/千克/天剂量的G-CSF直接给药，发现其可显著刺激GM-CFU形成并增加外周单个核细胞中c-kit+细胞。更重要的是，75毫戈瑞的X射线加150微克/千克/天的G-CSF（LDR/150-G-CSF）产生的效果与单独使用300微克/千克/天的G-CSF相似。此外，通过计数外周白细胞和CFUs-S，在致死性照射的受体小鼠中证实了LDR动员的供体HPC重建血细胞的能力。
这些结果表明，LDR可诱导造血兴奋效应，表现为HPC增殖和外周动员，为HPC外周动员的临床应用提供了一种潜在方法。
