Brain, Vol. 125, No. 4, 823-834,
April 2002
© 2002 Guarantors of Brain
Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10
1 Department of Neurology, Karl-Franzens-University, Graz, Austria, 2 Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany, 3 Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA, 4 Division of Biomedical Sciences, Sheffield Hallam University, Sheffield, UK, 5 Department of Neurology, Kyoto University, Kyoto, Japan, 6 Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA and 7 Department of Neurology, Julius-Maximilians-University, Würzburg, Germany
Correspondence to: B. C. Kieseier, Department of Neurology, Heinrich-Heine-University, Moorenstraße 5, 40225 Düsseldorf, Germany E-mail: bernd.kieseier{at}uni-duesseldorf.de
Inflammatory cell recruitment is an important step in the pathogenesis of autoimmune demyelinating diseases of the PNS. Chemokines might play a critical role in promoting leucocyte entry into the nervous system during immune-mediated inflammation. Here, we report the expression pattern of the chemokine receptors CCR-1, CCR-2, CCR-4, CCR-5 and CXCR-3 in sural nerve biopsies obtained from patients with classical Guillain–Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy), chronic inflammatory demyelinating polyradiculoneuropathy and various non-inflammatory neuropathies. A consistent chemokine receptor expression pattern was immunohistochemically detected in inflammatory demyelinating neuropathies and quantitation of labelled mononuclear cells revealed significantly elevated cell counts compared with controls. CCR-1 and CCR-5 were primarily expressed by endoneurial macrophages, whereas CCR-2, CCR-4 and CXCR-3 could be localized to invading T lymphocytes. Quantitative analysis revealed that CXCR-3 was expressed at highest numbers by infiltrating T cells compared with the other receptors. Thus, expression and distribution of CXCR-3 suggest a specific role of this receptor in chemokine-mediated lymphocyte traffic into the inflamed PNS tissue. Therefore, we further analysed the expression of its ligands interferon-
-inducible protein of 10 kDa (IP-10) and monokine induced by interferon- (Mig). Significantly increased levels of IP-10 could be measured in the CSF of patients with inflammatory neuropathies, whereas no differences were observable for Mig. In situ hybridization for IP-10 mRNA mirrored the distribution of the cognate receptor within the inflamed PNS, and delineated endothelial cells as the primary cellular source of IP-10. Our results imply a pathogenic role for specific chemokine receptors and IP-10 in the genesis of inflammatory demyelinating neuropathies.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H.-J. Kim, C.-G. Jung, M. A. Jensen, D. Dukala, and B. Soliven Targeting of Myelin Protein Zero in a Spontaneous Autoimmune Polyneuropathy J. Immunol., December 15, 2008; 181(12): 8753 - 8760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Hu, A. Janke, S. Ortler, H-P Hartung, C. Leder, B. C. Kieseier, and H. Wiendl Expression of CD28-related costimulatory molecule and its ligand in inflammatory neuropathies Neurology, January 23, 2007; 68(4): 277 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jiang, J. Xu, C. Zhou, Z. Wu, S. Zhong, J. Liu, W. Luo, T. Chen, Q. Qin, and P. Deng Characterization of Cytokine/Chemokine Profiles of Severe Acute Respiratory Syndrome Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 850 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Koller, B. C. Kieseier, S. Jander, and H.-P. Hartung Chronic Inflammatory Demyelinating Polyneuropathy N. Engl. J. Med., March 31, 2005; 352(13): 1343 - 1356. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wanschitz, H. Maier, H. Lassmann, H. Budka, and T. Berger Distinct time pattern of complement activation and cytotoxic T cell response in Guillain-Barre syndrome Brain, September 1, 2003; 126(9): 2034 - 2042. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D J Mahad, J Lawry, S J. Howell, and M N Woodroofe Longitudinal study of chemokine receptor expression on peripheral lymphocytes in multiple sclerosis: CXCR3 upregulation is associated with relapse Multiple Sclerosis, April 1, 2003; 9(2): 189 - 198. [Abstract] [PDF]
|
|
|
|
|
|
B. C. Kieseier, M. C. Dalakas, and H.-P. Hartung Immune mechanisms in chronic inflammatory demyelinating neuropathy Neurology, December 24, 2002; 59(90126): S7 - 12. [Abstract] [Full Text]
|
|
|
|
|
|
M. C. Dalakas Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies Neurology, December 24, 2002; 59(90126): S13 - 21. [Abstract] [Full Text]
|
|
|
|
 |
|
 D J Mahad, S J L Howell, and M N Woodroofe Expression of chemokines in cerebrospinal fluid and serum of patients with chronic inflammatory demyelinating polyneuropathy J. Neurol. Neurosurg. Psychiatry, September 1, 2002; 73(3): 320 - 323. [Abstract] [Full Text] [PDF]
|
|