Seki H, Kanegane H, Iwai K, Konno A, Ohta K, Yachie A, Taniguchi N, Miyawaki T
Department of Pediatrics, School of Medicine, Kanazawa University, Ishikawa, Japan.
Eur J Immunol. 1994 Nov;24(11):2914-7. doi: 10.1002/eji.1830241150.
The p53 tumor suppressor gene has been shown to be involved in programmed cell death, apoptosis, in murine immature thymocytes after treatment with ionizing radiation. Ionizing radiation also induces apoptosis in peripheral mature lymphocytes. In this work, we investigated the p53 participation in radiation-induced apoptosis in human peripheral blood lymphocytes (PBL) subpopulations. Exposure to gamma-irradiation resulted in an appreciable induction of apoptotic cell death in TcR-alpha/beta+ (CD4+ and CD8+) T cells, TcR-gamma/delta+ T cells, B cells and natural killer (NK) cells, as assessed by DNA fragmentation as well as the morphological characteristics. Importantly, it was found that there was a marked difference among PBL subpopulations as regards the induction of p53 protein by gamma-irradiation. Similar to previous observations for murine thymocytes, p53 induction in TcR-alpha/beta+ T cells and B cells after gamma-irradiation was evident by Western blot analysis. Radiation-induced apoptosis in TcR-alpha/beta+ T cells and B cells was efficiently inhibited by cycloheximide, indicating the requirement of de novo protein synthesis, including p53 protein, for radiation-induced apoptosis in both subpopulations. In marked contrast, no identifiable levels of p53 protein were induced in either TcR-gamma/delta+ T or NK cells after gamma-irradiation. In addition, it was demonstrated that radiation-induced cell death in TcR-gamma/delta+ T and NK cells could be prevented by interleukin-2, but not by cycloheximide. These results imply that radiation-induced lymphocytic apoptosis can be mediated by p53-dependent or -independent mechanisms.
p53肿瘤抑制基因已被证明在电离辐射处理后的小鼠未成熟胸腺细胞中参与程序性细胞死亡，即细胞凋亡。电离辐射也可诱导外周成熟淋巴细胞发生凋亡。在本研究中，我们调查了p53在人外周血淋巴细胞（PBL）亚群辐射诱导的凋亡中的作用。通过DNA片段化以及形态学特征评估，暴露于γ射线照射导致TcR-α/β+（CD4+和CD8+）T细胞、TcR-γ/δ+ T细胞、B细胞和自然杀伤（NK）细胞中凋亡性细胞死亡明显增加。重要的是，发现γ射线照射诱导p53蛋白在PBL亚群之间存在显著差异。与先前对小鼠胸腺细胞的观察结果相似，Western印迹分析显示γ射线照射后TcR-α/β+ T细胞和B细胞中p53的诱导明显。放线菌酮有效抑制了γ射线照射后TcR-α/β+ T细胞和B细胞中的辐射诱导凋亡，表明两个亚群中辐射诱导凋亡需要包括p53蛋白在内的从头蛋白质合成。与之形成鲜明对比的是，γ射线照射后，在TcR-γ/δ+ T细胞或NK细胞中均未诱导出可识别水平的p53蛋白。此外，还证明白细胞介素-2可预防γ射线照射诱导的TcR-γ/δ+ T细胞和NK细胞死亡，但放线菌酮不能。这些结果表明，辐射诱导的淋巴细胞凋亡可通过p53依赖性或非依赖性机制介导。
