Expression of DARC, CXCR3 and CCR5 in giant cell arteritis.
OBJECTIVE
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.
Brühl
H
H
Medical Policlinic, University of Munich, Munich, Germany. hilke.bruehl@med.uni-muenchen.de
Vielhauer
V
V
Weiss
M
M
Mack
M
M
Schlöndorff
D
D
Segerer
S
S
D015415:Biomarkers / Q000032:analysis; D018946:Chemokine CCL5 / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics; D004375:Duffy Blood-Group System / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D013700:Giant Cell Arteritis / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000737:chemistry; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D011111:Polymyalgia Rheumatica / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D019713:Receptors, CCR5 / Q000235:genetics*; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D013601:T-Lymphocytes / Q000737:chemistry; D013699:Temporal Arteries / Q000737:chemistry
C473745:ACKR1 protein, human; D015415:Biomarkers; C483024:CCL5 protein, human; C515187:CXCR3 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D004375:Duffy Blood-Group System; D012333:RNA, Messenger; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine