Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China; Marine Biology Lab, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Jiangsu 210093, China.
Cell Immunol. 2013 Nov-Dec;286(1-2):39-44. doi: 10.1016/j.cellimm.2013.10.002. Epub 2013 Oct 19.
Accumulating evidences suggested that mitochondrial uncoupling protein 2 (UCP2) is involved in host defense in parasite infection, inflammation, and autoimmune responses. However, it remains unknown whether UCP2 is participated in the modulation of humoral immune response. Here we used quantitative PCR, ELISA, TUNEL assay, flow cytometry, etc. to study the role of UCP2 in spleen B lymphocytes during pathogen activation and obtained following results. First, UCP2 is highly expressed in splenocytes and its expression level in splenocytes is rapidly increased when the cells are activated by lipopolysaccharide (LPS) in vivo or by LPS plus cytokines in vitro. Second, in contrast to the wild type (WT) littermates, the UCP2 knockout (UCP2-KO) mice show an impaired humoral immune response when they are challenged by pathogen. Although UCP2-KO mice produce a normal level of IgM, the levels of IgGs are significantly less than those of WT littermates. Third, splenocytes from UCP2-KO mice are more susceptible to pathogen activation-induced apoptosis, and the high level of reactive oxygen species (ROS) in UCP2-KO mice may be the cause for the apoptosis. In conclusion, our study demonstrates that mitochondrial UCP2 plays a critical role in protecting splenocytes from oxidative stress-induced apoptosis during pathogen activation.
越来越多的证据表明，线粒体解偶联蛋白 2（UCP2）参与寄生虫感染、炎症和自身免疫反应中的宿主防御。然而，UCP2 是否参与体液免疫反应的调节尚不清楚。在这里，我们使用定量 PCR、ELISA、TUNEL 检测、流式细胞术等方法研究 UCP2 在病原体激活过程中对脾 B 淋巴细胞的作用，得到以下结果。首先，UCP2 在脾细胞中高度表达，当细胞在体内被脂多糖（LPS）或体外被 LPS 和细胞因子激活时，其在脾细胞中的表达水平迅速增加。其次，与野生型（WT）同窝仔鼠相比，UCP2 敲除（UCP2-KO）鼠在受到病原体攻击时表现出受损的体液免疫反应。尽管 UCP2-KO 鼠产生正常水平的 IgM，但 IgG 的水平明显低于 WT 同窝仔鼠。第三，UCP2-KO 鼠的脾细胞更容易受到病原体激活诱导的细胞凋亡，而 UCP2-KO 鼠中高水平的活性氧（ROS）可能是细胞凋亡的原因。总之，我们的研究表明，线粒体 UCP2 在保护脾细胞免受病原体激活过程中氧化应激诱导的细胞凋亡方面起着关键作用。
