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on September 5, 2002

Arteriosclerosis, Thrombosis, and Vascular Biology. 2002
Published online before print September 5, 2002, doi: 10.1161/01.ATV.0000036418.04998.D5
A more recent version of this article appeared on November 1, 2002
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Submitted on August 7, 2002
Accepted on August 23, 2002

Endothelial Determinants of Dendritic Cell Adhesion and Migration. New Implications for Vascular Diseases

Michael Weis *; Christoph L. Schlichting ; Edgar G. Engleman ; and John P. Cooke

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.

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.


Key words: atherosclerosis • 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors • inflammation • nitric oxide




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