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Mediators of Inflammation
Volume 2012, Article ID 320953, 10 pages
http://dx.doi.org/10.1155/2012/320953
Research Article

oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21

1Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany
2Institute of Clinical Chemistry, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany
3Department of Surgery, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany
4Department of Cardiothoracic Surgery, J. W. Goethe University, 61590 Frankfurt, Germany
5Department of Cardiac Surgery, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany

Received 28 August 2011; Accepted 14 February 2012

Academic Editor: Carlos Henrique Serezani

Copyright © 2012 Thomas Nickel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction. 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. Methods and 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 . 0 1 )]. 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 . 0 5 ) and protein expression by 24% in HMECs by oxLDL ( 𝑃 < 0 . 0 5 ). 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.