title: Vascular oxidative stress increases dendritic cell adhesion and transmigration induced by homocysteine.
abstract: 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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zhu
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Le-Qing
authors.initials: LQ
authors.lastname: Lin
authors.forename: Hui
authors.initials: H
authors.lastname: Yan
authors.forename: Ting
authors.initials: T
authors.lastname: Fu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhu
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006710:Homocysteine