Szatmári Tünde, Persa Eszter, Kis Enikő, Benedek Anett, Hargitai Rita, Sáfrány Géza, Lumniczky Katalin
a Department of Radiation Medicine, Division of Radiobiology and Radiohygiene , National Public Health Institute , Budapest , Hungary.
Int J Radiat Biol. 2019 Jan;95(1):12-22. doi: 10.1080/09553002.2018.1450533. Epub 2018 Mar 29.
Radiation-induced bystander effects (RIBE) imply the involvement of complex signaling mechanisms, which can be mediated by extracellular vesicles (EVs). Using an in vivo model, we investigated EV-transmitted RIBE in blood plasma and radiation effects on plasma EV miRNA profiles.
C57Bl/6 mice were total-body irradiated with 0.1 and 2 Gy, bone marrow-derived EVs were isolated, and injected systemically into naive, 'bystander' animals. Proteome profiler antibody array membranes were used to detect alterations in plasma, both in directly irradiated and bystander mice. MiRNA profile of plasma EVs was determined by PCR array.
M-CSF and pentraxin-3 levels were increased in the blood of directly irradiated and bystander mice both after low and high dose irradiations, CXCL16 and lipocalin-2 increased after 2 Gy in directly irradiated and bystander mice, CCL5 and CCL11 changed in bystander mice only. Substantial overlap was found in the cellular pathways regulated by those miRNAs whose level were altered in EVs isolated from the plasma of mice irradiated with 0.1 and 2 Gy. Several of these pathways have already been associated with bystander responses.
Low and high dose effects overlapped both in EV-mediated alterations in signaling pathways leading to RIBE and in their systemic manifestations.
辐射诱导的旁观者效应（RIBE）意味着涉及复杂的信号传导机制，这可能由细胞外囊泡（EVs）介导。我们使用体内模型研究了血浆中EVs传递的RIBE以及辐射对血浆EV miRNA谱的影响。
对C57Bl/6小鼠进行0.1和2 Gy的全身照射，分离骨髓来源的EVs，并将其全身注射到未受照射的“旁观者”动物体内。使用蛋白质组分析抗体阵列膜检测直接受照射小鼠和旁观者小鼠血浆中的变化。通过PCR阵列测定血浆EVs的miRNA谱。
低剂量和高剂量照射后，直接受照射小鼠和旁观者小鼠血液中的M-CSF和五聚体-3水平均升高，直接受照射小鼠和旁观者小鼠在2 Gy照射后CXCL16和脂质运载蛋白-2升高，CCL5和CCL11仅在旁观者小鼠中发生变化。在从接受0.1和2 Gy照射的小鼠血浆中分离的EVs中，其水平发生改变的那些miRNA所调节的细胞途径中发现了大量重叠。这些途径中的几个已经与旁观者反应相关。
低剂量和高剂量效应在导致RIBE的信号通路的EV介导改变及其全身表现方面均有重叠。
