Abstract

Rationale

Natural killer (NK) cells play an important role in both the innate and adaptive arms of the immune system. While previous studies have demonstrated the effects of ionizing radiation on cytotoxic function of NK cells, little is known about how a chronic exposure to high LET alpha particles emitted by radionuclides will affect both NK population size and function. This study was conducted to determine the effects of ²²³RaCl₂ on splenic NK cell population size and function in Swiss Webster mice.

Methods

Swiss Webster mice were administered intravenously with 0, 50, or 600 kBq/kg ²²³RaCl₂. Spleens were harvested at 5, 12, and 19 days post-administration. The numbers of splenocytes per spleen were enumerated and flow cytometry was used to assess changes in the distribution of splenocyte subpopulations of B, CD4 and CD8 T lymphocytes, and NK cells. NK functional activity was quantified using YAC-1 target cells and the ⁵¹Cr-release assay.

Results

The total number of splenocytes was unaffected by ²²³RaCl₂. However, significant changes in the distribution of splenocyte subpopulations were observed for NK cells and CD8 T lymphocytes. NK functional activity was enhanced substantially relative to controls at 12 days post-administration, but decreased markedly by day 19.

Conclusion

NK functional activity is both diminished and enhanced by ²²³RaCl₂ depending on both administered activity and time post-administration. These results suggest that there may be an optimum window of time to combine the ²²³RaCl₂-induced antitumor NK cell response with other cancer therapies that elicit immune activation.

中文翻译：

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镭223二氯化物导致自然杀伤细胞群和细胞毒性功能的瞬时变化

摘要

基本原理

自然杀伤 (NK) 细胞在免疫系统的先天和适应性臂中都发挥着重要作用。虽然以前的研究已经证明了电离辐射对 NK 细胞的细胞毒性功能的影响，但对于长期暴露于放射性核素发射的高 LET α 粒子将如何影响 NK 种群大小和功能知之甚少。本研究旨在确定²²³ RaCl ₂对 Swiss Webster 小鼠脾脏 NK 细胞群大小和功能的影响。

方法

给瑞士韦伯斯特小鼠静脉注射 0、50 或 600 kBq/kg ²²³ RaCl ₂。在给药后 5、12 和 19 天收获脾脏。计算每个脾脏的脾细胞数量，并使用流式细胞术评估 B、CD4 和 CD8 T 淋巴细胞以及 NK 细胞的脾细胞亚群分布的变化。NK 功能活性使用 YAC-1 靶细胞和⁵¹ Cr 释放测定进行量化。

结果

脾细胞总数不受²²³ RaCl ₂影响。然而，在 NK 细胞和 CD8 T 淋巴细胞中观察到脾细胞亚群分布的显着变化。与对照组相比，NK 功能活性在给药后 12 天显着增强，但到第 19 天显着下降。

结论

NK 功能活性被²²³ RaCl ₂减弱和增强，这取决于给药后的活性和时间。^{这些结果表明，将223} RaCl ₂诱导的抗肿瘤 NK 细胞反应与引发免疫激活的其他癌症疗法相结合可能存在最佳时间窗口。