Zhu Wei-Guo, Li Shan, Lin Le-Qing, Yan Hui, Fu Ting, Zhu Jian-Hua
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
Cell Immunol. 2009;254(2):110-6. doi: 10.1016/j.cellimm.2008.08.001. Epub 2008 Sep 21.
Atherosclerosis is a long-term chronic inflammatory and immunological disease. Endothelial dysfunction and the dendritic cell (DC) immune response are pivotal early events in atherogenesis. This study investigated the effects and possible mechanisms of action of homocysteine (Hcy) on DC adhesion to and transmigration between endothelial cells (ECs), and indicated a novel immunoregulatory mechanism by which Hcy induces atherogenesis. When ECs were stimulated with increasing concentrations of Hcy, immunofluorescence showed that endothelial reactive oxygen species (ROS) generation strikingly increased, while nitrite assay showed that nitric oxide (NO) release markedly decreased. Furthermore, DC adhesion and transmigration were significantly increased when ECs were activated by Hcy. However, pretreatment of ECs with antioxidant before Hcy markedly attenuated the induction of DC adhesion and transmigration, dependent on the intracellular ROS decrease and endothelial NO increase. In conclusion, DC adhesion and transmigration are significantly increased by vascular oxidative stress under conditions of elevated Hcy levels. These findings provide insight into the inflammatory processes and immune responses occurring in atherosclerosis induced by Hcy.
动脉粥样硬化是一种长期的慢性炎症和免疫性疾病。内皮功能障碍和树突状细胞（DC）免疫反应是动脉粥样硬化发生过程中的关键早期事件。本研究调查了同型半胱氨酸（Hcy）对DC黏附于内皮细胞（ECs）以及在内皮细胞间迁移的影响及其可能的作用机制，并指出了一种Hcy诱导动脉粥样硬化的新型免疫调节机制。当用浓度递增的Hcy刺激ECs时，免疫荧光显示内皮细胞活性氧（ROS）生成显著增加，而亚硝酸盐检测显示一氧化氮（NO）释放明显减少。此外，当ECs被Hcy激活时，DC黏附和迁移显著增加。然而，在Hcy处理前用抗氧化剂预处理ECs可显著减弱DC黏附和迁移的诱导，这依赖于细胞内ROS减少和内皮细胞NO增加。总之，在Hcy水平升高的情况下，血管氧化应激显著增加DC黏附和迁移。这些发现为Hcy诱导的动脉粥样硬化中发生的炎症过程和免疫反应提供了见解。
