Kinetics of neutrophils in mice exposed to radiation and/or granulocyte colony-stimulating factor treatment.

Kinetics of neutrophils in mice exposed to radiation and/or granulocyte colony-stimulating factor treatment.
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DOI:
10.1667/rr3055.1
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发表时间:
2013-08
期刊:
影响因子:
3.4
通讯作者:
Kennedy AR
Kennedy AR
中科院分区:
医学3区
文献类型:
--
作者:
Romero-Weaver AL;Wan XS;Diffenderfer ES;Lin L;Kennedy AR

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宇航员在执行探测任务时,由于暴露在太阳粒子事件(SPE)的辐射中,有可能患上造血综合征。这种综合征的特点是循环血细胞数量减少(细胞减少)。在本研究中,以小鼠为模型系统,在一个月的时间内评估了sp样质子和γ辐射对循环中性粒细胞动力学的影响。结果显示,暴露于2 Gy剂量的sp样质子或γ辐射显著降低循环中性粒细胞的数量,在辐射后第4天和第16天观察到两个最低点。低循环中性粒细胞计数(中性粒细胞减少症)尤其重要,因为它会增加宇航员感染的风险,从而影响任务的成功。因此,两种粒细胞集落刺激因子(g - csf),非格昔汀和聚非格昔汀被评估为该终点的对策。两种形式的G-CSF均显著增加辐照小鼠的中性粒细胞计数,但聚非格昔汀的作用比非格昔汀更有效,持续时间更长。利用CD11b、CD18的表达和活性氧(ROS)的产生作为中性粒细胞活化的标志,确定聚非格昔亭辐照小鼠中性粒细胞具有生理活性。因此,这些结果表明,聚非格司提姆可能是一个潜在的对策,减少循环中性粒细胞在辐照动物的数量。
Astronauts have the potential to develop the hematopoietic syndrome as a result of exposure to radiation from a solar particle event (SPE) during exploration class missions. This syndrome is characterized by a reduction in the number of circulating blood cells (cytopenias). In the present study the effects of SPE-like proton and γ radiation on the kinetics of circulating neutrophils were evaluated during a one-month time period using mice as a model system. The results revealed that exposure to a 2 Gy dose of either SPE-like proton or γ radiation significantly decreased the number of circulating neutrophils, with two nadirs observed on day 4 and day 16 postirradiation. Low circulating neutrophil count (neutropenia) is particularly important because it can increase the risk of astronauts developing infections, which can compromise the success of the mission. Thus, two granulocyte colony-stimulating factors (G-CSFs), filgrastim and pegfilgrastim were evaluated as countermeasures for this endpoint. Both forms of G-CSF significantly increased neutrophil counts in irradiated mice, however, the effect of pegfilgrastim was more potent and lasted longer than filgrastim. Using the expression of CD11b, CD18 and the production of reactive oxygen species (ROS) as markers of neutrophil activation, it was determined that the neutrophils in the irradiated mice treated with pegfilgrastim were physiologically active. Thus, these results suggest that pegfilgrastim could be a potential countermeasure for the reduced number of circulating neutrophils in irradiated animals.