Adrenaline administration promotes the efficiency of granulocyte colony stimulating factor-mediated hematopoietic stem and progenitor cell mobilization in mice
Adrenaline administration promotes the efficiency of granulocyte colony stimulating factor-mediated hematopoietic stem and progenitor cell mobilization in mice
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肾上腺素给药促进小鼠粒细胞集落刺激因子介导的造血干细胞和祖细胞动员的效率
DOI：
10.1007/s12185-012-1228-1
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发表时间：
2013-01-01
影响因子：
2.1
通讯作者：
Xu, Kailin
中科院分区：
文献类型：
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作者：
Chen, Chong;Cao, Jiang;Xu, Kailin
大剂量粒细胞集落刺激因子（G-CSF）被广泛用于动员造血干细胞和祖细胞（HSPC），但G-CSF相对低效且可能引起不良反应。最近，肾上腺素已被发现在HSPC动员中发挥重要作用。在这项研究中，我们探讨了肾上腺素与G-CSF组合是否可以在小鼠模型中诱导HSPC动员。用肾上腺素和高剂量或低剂量的G-CSF单独或组合处理小鼠。通过流式细胞术评价外周血HSPC计数。ELISA法检测骨髓基质细胞衍生因子-1（SDF-1）的表达水平，实时荧光定量RT-PCR法检测CXCR 4和SDF-1的转录水平，Western blot法检测CXCR 4蛋白的表达。我们的结果表明，单独的肾上腺素不能动员HSPC进入外周血;然而，当G-CSF和肾上腺素组合时，与单独接受G-CSF的小鼠相比，WBC计数和HSPC百分比显著更高。肾上腺素和G-CSF的联合使用不仅加速了HSPC动员，而且在较低剂量的G-CSF下能够有效地将HSPC动员到外周血中。肾上腺素/G-CSF治疗也广泛下调小鼠骨髓中SDF-1和CXCR 4的水平。这些结果表明，肾上腺素联合G-CSF可通过下调CXCR 4/SDF-1轴诱导HSPC动员，表明使用肾上腺素可减少G-CSF治疗的剂量或持续时间，从而最大限度地减少G-CSF相关并发症。
A high dose of granulocyte colony stimulating factor (G-CSF) is widely used to mobilize hematopoietic stem and progenitor cells (HSPC), but G-CSF is relatively inefficient and may cause adverse effects. Recently, adrenaline has been found to play important roles in HSPC mobilization. In this study, we explored whether adrenaline combined with G-CSF could induce HSPC mobilization in a mouse model. Mice were treated with adrenaline and either a high or low dose of G-CSF alone or in combination. Peripheral blood HSPC counts were evaluated by flow cytometry. Levels of bone marrow SDF-1 were measured by ELISA, the transcription of CXCR4 and SDF-1 was measured by real-time RT-PCR, and CXCR4 protein was detected by Western blot. Our results showed that adrenaline alone fails to mobilize HSPCs into the peripheral blood; however, when G-CSF and adrenaline are combined, the WBC counts and percentages of HSPCs are significantly higher compared to those in mice that received G-CSF alone. The combined use of adrenaline and G-CSF not only accelerated HSPC mobilization, but also enabled the efficient mobilization of HSPCs into the peripheral blood at lower doses of G-CSF. Adrenaline/G-CSF treatment also extensively downregulated levels of SDF-1 and CXCR4 in mouse bone marrow. These results demonstrated that adrenaline combined with G-CSF can induce HSPC mobilization by down-regulating the CXCR4/SDF-1 axis, indicating that the use of adrenaline may enable the use of reduced dosages or durations of G-CSF treatment, minimizing G-CSF-associated complications.