Endothelial determinants of dendritic cell adhesion and migration: New implications for vascular diseases

Michael Weis, Christoph L. Schlichting, Edgar G. Engleman, John P. Cooke

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

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-α. 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.

Original languageEnglish (US)
Pages (from-to)1817-1823
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2002

Keywords

  • 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
  • Atherosclerosis
  • Inflammation
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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