Department of Physics, IK Barber Faculty of Science, University of British Columbia Okanagan, Kelowna, Canada V1V 1V7.
Radiat Res. 2021 Sep 1;196(3):297-305. doi: 10.1667/RADE-20-00291.1.
Survival from partial-body irradiation (PBI) may be limited by the development of the late lung injury response of pneumonitis. Herein we investigated the hypothesis that acute hematopoietic depletion alters the onset and severity of lung disease in a mouse model. To establish depletion, C3H/HeJ mice received 8 Gy PBI with shielding of only the tibiae, ankles and feet. One week after irradiation, blood lymphocyte and neutrophil counts were each significantly reduced (P < 0.04) in these mice compared to levels in untreated controls or in mice receiving 16 Gy to the whole thorax only. All 8 Gy PBI mice survived to the experimental end point of 16 weeks postirradiation. To determine whether the hematopoietic depletion affects lung disease, groups of mice received 8 Gy PBI plus 8 Gy whole-thorax irradiation (total lung dose of 16 Gy) or 16 Gy whole-thorax irradiation only. The weight loss, survival to onset of respiratory distress (P = 0.17) and pneumonitis score (P = 0.96) of mice that received 8 Gy PBI plus 8 Gy whole-thorax irradiation were not significantly different from those of mice receiving 16 Gy whole-thorax irradiation only. Mice in respiratory distress from PBI plus whole-thorax irradiation had significantly reduced (P = 0.02) blood monocyte counts compared to levels in distressed, whole-thorax irradiated mice, and symptomatic pneumonitis was associated with increased blood neutrophil counts (P = 0.04) relative to measures from irradiated, non-distressed mice. In conclusion, survivable acute hematopoietic depletion by partial-body irradiation did not alter the onset or severity of lethal pneumonitis in the C3H/HeJ mouse model.
从半身照射(PBI)的存活率可能受到放射性肺炎的晚期肺损伤反应的发展限制。在此,我们研究了以下假设:急性造血细胞耗竭会改变小鼠模型中肺部疾病的发病和严重程度。为了建立耗竭模型,C3H/HeJ 小鼠仅对胫骨、踝关节和足部进行 8GyPBI 照射,并在照射后 1 周,与未处理的对照组或仅接受全胸 16Gy 照射的小鼠相比,这些小鼠的血液淋巴细胞和中性粒细胞计数均显著降低(P<0.04)。所有 8GyPBI 小鼠均存活至照射后 16 周的实验终点。为了确定造血细胞耗竭是否影响肺部疾病,将小鼠分为接受 8GyPBI 加 8Gy 全胸照射(总肺剂量为 16Gy)或仅接受 16Gy 全胸照射的两组。接受 8GyPBI 加 8Gy 全胸照射的小鼠的体重减轻、呼吸窘迫发病的存活率(P=0.17)和放射性肺炎评分(P=0.96)与仅接受 16Gy 全胸照射的小鼠无显著差异。与仅接受全胸照射的呼吸困难的小鼠相比,接受 PBI 加全胸照射的小鼠的血液单核细胞计数显著降低(P=0.02),并且症状性放射性肺炎与血液中性粒细胞计数增加(P=0.04)相关,与照射后无症状的小鼠相比,这些测量值增加。总之,通过半身照射实现可存活的急性造血细胞耗竭并未改变 C3H/HeJ 小鼠模型中致死性放射性肺炎的发病或严重程度。