Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation
Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation
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DOI：
10.1016/j.exphem.2004.07.015
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发表时间：
2004-11-01
影响因子：
2.6
通讯作者：
Cai, L
中科院分区：
文献类型：
--
作者：
Li, W;Wang, GJ;Cai, L
目标。本研究旨在探讨低剂量辐射(LDR)对骨髓造血祖细胞(HPC)增殖和外周血动员的刺激作用。小鼠接受25mGy到100mGyX射线照射。检测骨髓和外周血造血祖细胞(BFU-E、CFU-GM和c-kit(+)细胞)，用ELISA法、狭缝印迹杂交法和Northern印迹法检测GM-CSF、G-CSF和IL-3蛋白和mRNA的表达。为了从功能上评估LDR刺激和动员的HPC，采用白细胞计数、动物存活率和受体脾中集落形成单位(CFU-S)来检测接受致死性照射的受者移植后外周血细胞的再聚集情况。75 mGyX射线照射后48小时对骨髓HPC增殖(CFU-GM和BFU-E形成)的刺激作用最强，照射后48-72小时外周血中HPC的动员显著增加，表现为CFU-GM的形成和外周血中c-kit+细胞比例的增加。75mGyX射线还可最大限度地诱导脾细胞G-CSF和GM-CSF mRNA表达增加以及血清GM-CSF水平升高。为了明确这些造血刺激因子在HPC动员中的关键作用，直接给予G-CSF 300µg/kg/天或150µg/kg/天，可显著刺激GM-CFU的形成，并增加外周血单个核细胞中的c-kit(+)细胞。更重要的是，75mGyX射线加150µg/kg/d G-CSF(LDR/150-G-CSF)产生的效果与单独使用300µg/kg/d G-CSF的效果相似。此外，通过计数外周血WBC和CFU-S，证实了LDR动员的供体HPC在致死性照射的受体小鼠中重新填充血细胞的能力。这些结果表明，LDR可以诱导造血刺激，表现为HPC的增殖和外周血动员，为HPC外周血动员的临床应用提供了一条潜在的途径。(C)2004年国际实验血液学学会。由爱思唯尔公司出版。
Objective. 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.Methods. 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).Results. 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 mug/kg/day or 150 mug/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 mug/kg/day G-CSF (LDR/150-G-CSF) produced a similar effect to that of 300 mug/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.Conclusion. 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. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc.