Rheumatology Advance Access originally published online on July 6, 2007
Rheumatology 2007 46(9):1422-1427; doi:10.1093/rheumatology/kem168
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Increased expression of fractalkine (CX3CL1) and its receptor, CX3CR1, in Wegener's granulomatosis—possible role in vascular inflammation
1Research Institute for Internal Medicine, Faculty Division Rikshospitalet, University of Oslo and 2Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet-Radiumhospitalet Medical Center and Faculty Division Rikshospitalet, University of Oslo, N-0027 Oslo, Norway.
Correspondence to: Vigdis Bjerkeli, Research Institute for Internal Medicine, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, 0027 Oslo, Norway. E-mail: vigdis.bjerkeli{at}medisin.uio.no
 |
Abstract |
|---|
Objective. Based on the function of fractalkine (CX3CL1), the unique member of the CX3C chemokine subfamily, in endothelial-related inflammation, we hypothesized a role for CX3CL1 and its receptor (CX3CR) in Wegener's granulomatosis (WG). In the present study, this hypothesis was tested by different experimental approaches.
Methods. We examined plasma levels of CX3CL1 (enzyme immunoassay) and CX3CR1 expression in peripheral blood mononuclear cells (PBMCs) (real-time quantitative RT-PCR and flow cytometry) in 18 WG patients and 15 healthy controls. In eight of these individuals, we also examined CX3CR1-mediated chemotaxis and adhesion in T cells and monocytes as well as the effects of CX3CL1 on monocyte chemoattractant protein (MCP) 1 levels in PBMC supernatants.
Results. Our main findings were: (i) WG patients had markedly increased plasma levels of CX3CL1, with particularly high levels in those with active disease, (ii) These increased CX3CL1 levels were accompanied by enhanced expression of its corresponding receptor, CX3XR1, in PBMC, primarily reflecting an increased proportion of CX3CR1+CD3+CD4+ T cells and (iii) The up-regulation of CX3CR1 in PBMC from WG patients affected their functional potential as shown by CX3CL1-induced enhancement of chemotaxis, adhesion, responses as well as MCP-1 stimulation.
Conclusion. Based on the ability of CX3CL1 to promote leucocyte infiltration into the vessel wall of inflammatory levels, it is tempting to hypothesize that increased CX3CL1/CX3CR1 interaction could be involved in the pathogenesis of the granulomatous vasculitis characterizing WG.
KEY WORDS: Wegener's granulomatosis, Fractalkine, Chemokines, Inflammation, Mononuclear cells
Submitted 6 March 2007;
revised version accepted 18 May 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. BLASCHKE, P. BRANDT, J. T. WESSELS, and G. A. MULLER Expression and Function of the C-Class Chemokine Lymphotactin (XCL1) in Wegener's Granulomatosis J Rheumatol, November 1, 2009; 36(11): 2491 - 2500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Wilde, P. van Paassen, J. Damoiseaux, P. Heerings-Rewinkel, H. van Rie, O. Witzke, and J. W. C. Tervaert Dendritic cells in renal biopsies of patients with ANCA-associated vasculitis Nephrol. Dial. Transplant., July 1, 2009; 24(7): 2151 - 2156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. ODAI, M. MATSUNAWA, R. TAKAHASHI, K. WAKABAYASHI, T. ISOZAKI, N. YAJIMA, Y. MIWA, and T. KASAMA Correlation of CX3CL1 and CX3CR1 Levels with Response to Infliximab Therapy in Patients with Rheumatoid Arthritis J Rheumatol, June 1, 2009; 36(6): 1158 - 1165. [Abstract] [Full Text] [PDF]
|
|