title: oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.
abstract: BACKGROUND
  Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21.
  
  
  RESULTS
  The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (P < 0.01)]. In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (P < 0.05) and protein expression by 24% in HMECs by oxLDL (P < 0.05).
  
  
  CONCLUSIONS
  The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques.
authors.affiliation: Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany. tsnickel@web.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Nickel
authors.forename: Susanne
authors.initials: S
authors.lastname: Pfeiler
authors.forename: Claudia
authors.initials: C
authors.lastname: Summo
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kopp
authors.forename: Georgios
authors.initials: G
authors.lastname: Meimarakis
authors.forename: Zeljka
authors.initials: Z
authors.lastname: Sicic
authors.forename: Marius
authors.initials: M
authors.lastname: Lambert
authors.forename: Korbinian
authors.initials: K
authors.lastname: Lackermair
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Andres
authors.initials: A
authors.lastname: Beiras-Fernandez
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
mesh_terms: D050197:Atherosclerosis / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology*; D018450:Disease Progression; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008833:Microcirculation; D008856:Microscopy, Fluorescence / Q000379:methods; D009000:Monocytes / Q000166:cytology; D054400:Receptors, CCR7 / Q000378:metabolism*
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D008024:Ligands; D008077:Lipoproteins, LDL; D054400:Receptors, CCR7; C099252:oxidized low density lipoprotein