title: Endothelial determinants of dendritic cell adhesion and migration: new implications for vascular diseases.
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.
  
  
  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.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif, USA. miweis@med.uni-muenchen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
authors.forename: Christoph L
authors.initials: CL
authors.lastname: Schlichting
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
mesh_terms: D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000502:physiology; D039521:CD11c Antigen / Q000096:biosynthesis; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004727:Endothelium / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010101:Oxygen Consumption / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000166:cytology; D013234:Stem Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology
chemical_list: D039521:CD11c Antigen; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III