Chen Xiaolong, Zheng Jun, Cai Jianye, Li Hui, Li Shihui, Wang Li, Cheng Daorou, Chen Huaxin, Yang Yang, Chen Guihua, Zhang Qi, Peng Yanwen, Wang Qiyou, Wang Genshu
Department of Hepatic Surgery, Liver Transplantation, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, Guangdong Province, China.
Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630, Guangdong Province, China.
Am J Transl Res. 2017 Nov 15;9(11):4888-4901. eCollection 2017.
Cytoskeletal proteins and associated regulatory proteins are essential for maintaining cell structure and growth. β-actin is a major component of the cytoskeleton, and β-actin remodeling is involved in lymphocyte migration, infiltration and apoptosis. However, little is known about whether changes in β-actin expression affect lymphocyte cell fate, particularly during acute rejection after liver transplantation in a rat model. In our studies, grafts were harvested on days 5, 7 or 9 after xenogeneic rat liver transplantation. The acute rejection grade was histopathologically evaluated. Recipient-derived CD8 T lymphocytes gradually infiltrated into liver allografts in cases of severe acute rejection. The apoptotic rate of CD8 T lymphocytes peaked on day 7 and then decreased. Moreover, changes in β-actin expression were consistent with the apoptotic rate of CD8 T lymphocytes in both allografts and peripheral blood based on western blotting and immunohistochemistry results. Additionally, jasplakinolide (an actin-stabilizing drug) evoked CD8 T lymphocyte apoptosis. In conclusion, our study is the first to describe the fluctuating expression levels and dynamics of the cytoskeletal protein β-actin and its potential roles in the pathogenesis of acute rejection following rat liver transplantion. Our results enhance the understanding of the roles of CD8 T lymphocytes during acute rejection and suggest that β-actin regulation leads to apoptosis.
细胞骨架蛋白及相关调节蛋白对于维持细胞结构和生长至关重要。β-肌动蛋白是细胞骨架的主要成分,β-肌动蛋白重塑参与淋巴细胞迁移、浸润和凋亡。然而,关于β-肌动蛋白表达的变化是否影响淋巴细胞命运,尤其是在大鼠肝移植急性排斥反应期间,人们了解甚少。在我们的研究中,在异种大鼠肝移植后第5、7或9天采集移植物。通过组织病理学评估急性排斥反应分级。在严重急性排斥反应病例中,受体来源的CD8 T淋巴细胞逐渐浸润到肝同种异体移植物中。CD8 T淋巴细胞的凋亡率在第7天达到峰值,然后下降。此外,基于蛋白质印迹法和免疫组织化学结果,β-肌动蛋白表达的变化与同种异体移植物和外周血中CD8 T淋巴细胞的凋亡率一致。此外,茉莉酮酸酯(一种肌动蛋白稳定药物)可诱导CD8 T淋巴细胞凋亡。总之,我们的研究首次描述了细胞骨架蛋白β-肌动蛋白的波动表达水平和动态变化及其在大鼠肝移植后急性排斥反应发病机制中的潜在作用。我们的结果增进了对CD8 T淋巴细胞在急性排斥反应中作用的理解,并表明β-肌动蛋白调节导致细胞凋亡。