Vascular oxidative stress increases dendritic cell adhesion and transmigration induced by homocysteine.
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.
Zhu
Wei-Guo
WG
Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, China.
Li
Shan
S
Lin
Le-Qing
LQ
Yan
Hui
H
Fu
Ting
T
Zhu
Jian-Hua
JH
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
D017382:Reactive Oxygen Species; D006710:Homocysteine