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Submitted on August 7, 2002
Accepted on August 23, 2002
From the Division of Cardiovascular Medicine (M.W., J.P.C.) and the Departments of Pathology and Medicine (C.L.S., E.G.E.), Stanford University School of Medicine, Stanford, Calif, and Medizinische Klinik I (M.W.), University Hospital Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.
* To whom correspondence should be addressed. E-mail: miweis{at}med.uni-muenchen.de.
ObjectiveAtherosclerosis 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 ResultsWe 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-
. 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.
ConclusionsThe 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.
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