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Rheumatology Advance Access originally published online on November 30, 2004
Rheumatology 2005 44(3):309-313; doi:10.1093/rheumatology/keh485
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Rheumatology Vol. 44 No. 3 © British Society for Rheumatology 2004; all rights reserved

Expression of DARC, CXCR3 and CCR5 in giant cell arteritis

H. Brühl, V. Vielhauer, M. Weiss1, M. Mack, D. Schlöndorff and S. Segerer

Medical Policlinic and 1 Institute of Pathology, University of Munich, Munich, Germany.

Correspondence to: H. Brühl, Medical Policlinic, University of Munich, Schillerstrasse 42, 80336 Munich, Germany. E-mail: hilke.bruehl{at}med.uni-muenchen.de

Objectives. Leucocyte infiltration is the hallmark of vasculitis, chemokines being mainly responsible for leucocyte migration into inflamed tissues. The objective was to evaluate the local expression of chemokines and chemokine receptors in biopsies of patients with giant cell arteritis (GCA) compared with arteries from patients with polymyalgia rheumatica (PMR). We studied the expression of CCR5, CXCR3 and that of the Duffy antigen/receptor of chemokine (DARC), a chemokine internalizing receptor (interceptor), in parallel to the expression of the CCR5 ligand RANTES/CCL5.

Methods. Paraffin-embedded tissue sections from six patients with GCA and five patients with PMR were available for immunohistological analysis of chemokine receptor expression. RANTES/CCL5 mRNA was detected in tissue sections by in situ hybridization.

Results. In patients with biopsy-proven giant cell arteritis, CCR5 and CXCR3 were highly expressed by infiltrating leucocytes in involved tissue sections. Predominant clustering of CCR5+ and CXCR3+ leucocytes was found in the adventitia and was co-localized with the expression of CCL5/RANTES mRNA. Interestingly, we found marked expression of DARC on adventitial high endothelial venules in vasculitis lesions of patients with GCA, while in arteries from patients with PMR DARC was only expressed on a low number of vessels with flat lining endothelium.

Conclusions. The co-localization of infiltrating CCR5+ and CXCR3+ leucocytes together with CCL5/RANTES and DARC in vasculitis lesions suggests a role for these chemokine receptors in leucocyte infiltration, possibly supported by DARC-mediated vascular presentation of chemokines.

KEY WORDS: Giant cell arteritis, Chemokine, Chemokine receptor, DARC, Duffy antigen receptor for chemokines, CCR5, CXCR3, CCL5, RANTES


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