OBJECTIVE: Atherosclerosis is a chronic disease triggered by endothelial injury and sustained by inflammation. Dendritic cells (DCs) are critical for the cell-mediated arm of an immune response and are known to influence inflammatory immunity. A fundamental aspect of DC function is their capacity to adhere and migrate through vascular endothelial cells (ECs). We investigated the role of endothelial activation and dysregulation of the NO pathway on DC adhesion and migration. METHODS AND RESULTS: We discovered that DC adhesion and migration are modulated by changes in endothelial function. DC adhesion and transmigration were markedly increased after exposing ECs to hypoxia, oxidized low density lipoprotein, or tumor necrosis factor-alpha. Specifically, inhibition of endothelial NO synthase increased DC binding and transmigration. L-Arginine or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition partially decreased DC-EC interaction. CONCLUSIONS: The results of this study suggest that the adhesion and migration of DCs are increased by stimuli known to accelerate atherogenesis. Vice versa, augmentation of endothelial NO synthase activity prevents DC adhesion. These findings may provide insight into the inflammatory processes occurring in atherosclerosis. Because DCs control immunity, regulating DC-EC interaction may be relevant to inflammation and atherogenesis.
OBJECTIVE:Atherosclerosis is a chronic disease triggered by endothelial injury and sustained by inflammation. Dendritic cells (DCs) are critical for the cell-mediated arm of an immune response and are known to influence inflammatory immunity. A fundamental aspect of DC function is their capacity to adhere and migrate through vascular endothelial cells (ECs). We investigated the role of endothelial activation and dysregulation of the NO pathway on DC adhesion and migration. METHODS AND RESULTS: We discovered that DC adhesion and migration are modulated by changes in endothelial function. DC adhesion and transmigration were markedly increased after exposing ECs to hypoxia, oxidized low density lipoprotein, or tumor necrosis factor-alpha. Specifically, inhibition of endothelial NO synthase increased DC binding and transmigration. L-Arginine or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition partially decreased DC-EC interaction. CONCLUSIONS: The results of this study suggest that the adhesion and migration of DCs are increased by stimuli known to accelerate atherogenesis. Vice versa, augmentation of endothelial NO synthase activity prevents DC adhesion. These findings may provide insight into the inflammatory processes occurring in atherosclerosis. Because DCs control immunity, regulating DC-EC interaction may be relevant to inflammation and atherogenesis.
Authors: Julio Carrion; Elizabeth Scisci; Brodie Miles; Gregory J Sabino; Amir E Zeituni; Ying Gu; Adam Bear; Caroline A Genco; David L Brown; Christopher W Cutler Journal: J Immunol Date: 2012-08-13 Impact factor: 5.422
Authors: Andrew G Masoud; Jiaxin Lin; Abul K Azad; Maikel A Farhan; Conrad Fischer; Lin F Zhu; Hao Zhang; Banu Sis; Zamaneh Kassiri; Ronald B Moore; Daniel Kim; Colin C Anderson; John C Vederas; Benjamin A Adam; Gavin Y Oudit; Allan G Murray Journal: J Clin Invest Date: 2020-01-02 Impact factor: 14.808
Authors: Peter F Bove; Milena Hristova; Umadevi V Wesley; Nels Olson; Karen M Lounsbury; Albert van der Vliet Journal: J Biol Chem Date: 2008-04-18 Impact factor: 5.157