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The Role of Chemokines in the Pathogenesis of Multiple Sclerosis

  • Chapter
The Functional Roles of Glial Cells in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 468))

Abstract

Chemokines are a rapidly expanding family of small, secreted, 8-12 kDa, heparin-binding chemotactic cytokines, which are important in the pathogenesis of immune-mediated inflammation in the central nervous system (CNS) (Karpus et al., 1994). Chemokines mediate the activation and directional migration of inflammatory cells, including neutrophils, monocytes, T-lymphocytes, basophils, and eosinophils, to sites of injury and inflammation (Baggiolini, 1998). To date, they are divided into at least four families depending on the presence and position of a conserved motif of four cysteine residues. The majority of known chemokines are members of the CXC (α-chemokine) or CC (β-chemokine) families. Two further classes of chemokines, C and CX3C, have recently been reported, of which lymphotactin and neurotactin, respectively, are the only known members (Taub, 1996; Baggiolini, 1998). α-chemokines primarily chemoattract neutrophils, whereas β-chemokines are associated with chronic inflammation and are primarily involved in the recruitment of monocytes and T-lymphocytes to sites of inflammation. The β-chemokines include macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-l, MCP-2, MCP-3, and RANTES (regulated upon activation, normal T-cell expressed and secreted) (Vaddi et al., 1996).

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References

  • Baggiolini, M. (1998) Chemokines and leukocyte trafficking. Nature 392: 565–568.

    Article  PubMed  CAS  Google Scholar 

  • Barnes, D.A., Huston M., Holmes R., Benveniste, E.N., Yong, V.W., Scholz P., and Perez, H.D. (1996) Induction of RANTES expression by astrocytes and astrocytoma cell lines. J. Neuroimmunol. 71: 207–214.

    Article  PubMed  CAS  Google Scholar 

  • Benveniste, E.N. (1997) Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med. 75: 165–173.

    Article  PubMed  CAS  Google Scholar 

  • Berman, J.W., Guida, M.P., Warren J., Amat J., and Brosnan, C.E (1996) Localisation of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J. Immunol. 156: 3017–3023.

    PubMed  CAS  Google Scholar 

  • Bradl, M. and Linington, C. (1996) Animal models of demyelination. Brain Pathol. 6: 303–311.

    Article  PubMed  CAS  Google Scholar 

  • Brosnan, C.E and Raine, C.S. (1996) Mechanisms of immune injury in multiple sclerosis. Brain Path. 6: 243–257.

    Article  CAS  Google Scholar 

  • Calvo, C-E, Yoshimura, T., Gelman M., and Mallat, M. (1996) Production of monocyte chemotactic protein1 by rat brain macrophages. Eur. J Neurosci. 8: 1725–1734.

    Article  PubMed  CAS  Google Scholar 

  • Campbell, J.J., Foxman, E.E, and Butcher, E.C. (1997) Chemoattractant receptor cross talk as a mechanism in leukocyte adhesion and migration. Eur. X Immunol. 27: 2571–2578.

    Article  CAS  Google Scholar 

  • Cross A.K., Richardson V., Ali, S.A., Palmer I., Taub, D.D., and Rees, R.C. (1997) Migration responses of human monocytic cell lines to α-and β-chemokines. Cytokine 9: 521–528.

    Article  PubMed  CAS  Google Scholar 

  • Cuzner, M.L., Gveris D., Strand C., Loughlin, A.J., Paemen L., Opdenakker G., and Newcombe, J. (1996) The expression of tissue type plasminogen activator, matrix metalloproteases, and endogenous inhibitors in the central nervous system in multiple sclerosis: Comparison of stages in lesion evolution. J Neuropathol. and Exptl. Neurol. 55(12): 1194–1204.

    Article  CAS  Google Scholar 

  • Dickson, D.W., Lee, S.C., Mattiace, L.A., Yen, S.C., and Brosnan, C. (1993) Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer’s disease. Glia 7: 75–83.

    Article  PubMed  CAS  Google Scholar 

  • Ghirnikar, R.S., Lee, Y.L., He, T.R., and Eng, L.F. (1996) Chemokine expression in rat stab wound brain injury. J. Neurosci. Res. 46: 727–733.

    Article  PubMed  CAS  Google Scholar 

  • Glabinski, A.R., Tani M., Aras S., Stoler, M.H., Tuohy, V.K., and Ransohoff, R.M. (1995) Regulation and function of central nervous system chemokines. Int. J Dev. Neurosci. 13: 153–165.

    Article  PubMed  CAS  Google Scholar 

  • Glabinski, A.R., Balasingam V., Tani M., Kunkel, S.L., Strieter, R.M., Yong, V.W., and Ransohoff, R.M. (1996) Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J Immunol. 156: 4363–4368.

    PubMed  CAS  Google Scholar 

  • Godiska R., Chantry D., Dietsch, G.N., and Gray, P.W. (1995) Chemokine expression in murine experimental allergic encephalomyelitis. J. Neurimmunol. 58: 167–176.

    Article  CAS  Google Scholar 

  • Greenwood J., Pryce G., Devine L., Male D., dos Santos W., Calder V., and Adamson, P. (1996) SV40 large T transformed cell lines of the blood brain and blood retinal barriers retain their phenotypic and immunological characteristics. J. Neuroimmunology 71: 51–63.

    Article  CAS  Google Scholar 

  • Hayashi M., Luo, Y, Laning J., Strieter, R.M., and Dorf, M.E. (1995) Production and function of monocyte chemoattractant protein-1 and other beta chemokines in murine glial cells. J. Neuroimmunol. 60: 143–150.

    Article  PubMed  CAS  Google Scholar 

  • Hayes, G.M., Woodroofe, M.N., and Cuzner, M.L. (1988) Characterisation of microglia isolated from adult human and rat brain. J Neuroimmunol 19: 177–189.

    Article  PubMed  CAS  Google Scholar 

  • He, J, Chen Y., Farzan M., Choe H., Ohagen A., Gartner S., Busciglio J., Yang X., Hofmann W., Newman W., Mackay, C.R., Sodroski W., and Gabuzda, D. (1997) CCR3 and CCR5 are co-receptors for HIV1 infection of microglia. Nature 385: 645–649.

    Article  PubMed  CAS  Google Scholar 

  • Hulkower K., Brosnan, C.E, Aquino, D.A., Cammer W., Kulshrestha S., Guida, M.P, Rapoport, D.A., and Berman, J.W. (1993) Expression of CSF-1, c-fms, and MCP-1 in the central nervous system of rats with experimental allergic encephalomyelitis. J. Immunol. 150: 2525–2533.

    PubMed  CAS  Google Scholar 

  • Jiang, Y.L., Beller, D.I., Frendl G., and Graves, D.T. (1992) Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J. Immunol. 148: 2423–2428.

    PubMed  CAS  Google Scholar 

  • Karpus, W.J., Lukacs, N.W., McRae, B.L., Strieter, R.M., Kunkel, S.L., and Miller, S.D. (1995) An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T-cell-mediated autoimmune-disease experimental allergic encephalomyelitis. J. Immunol. 155: 5003–5010.

    PubMed  CAS  Google Scholar 

  • Kuna P., Reddigari, S.R., Schall, TJ, Rucinski D., Sadick M., and Kaplan, A.P. (1993) Characterisation of the human basophil response to cytokines, growth factors, and histamine releasing factors of the intercrine/chemokine family. J. Immunol. 150: 1932–1943.

    PubMed  CAS  Google Scholar 

  • Lloyd, A.R., Oppenheim, J.J., Kelvin, D.J., and Taub, D.D. (1996) Chemokines regulate T cell adherence to recombinant adhesion molecules and extracellular matrix proteins. J. Immunol. 156: 932–958.

    PubMed  CAS  Google Scholar 

  • Marfaing-Koka A., Devergne O., Gorgone G., Portier A., Schall T., Galanaud P., and Emilie, D. (1995) Regulation annd production of the RANTES chemokine by endothelial cells. Synergistic induction by IFN-γ plus TNF-α and inhibition by IL-4 and IL-13. J. Immunol. 154:1870–1878.

    PubMed  CAS  Google Scholar 

  • McCombe, PA., de Jersey J., and Pender, M.P (1994) Inflammatory cells, microglia and MHC class II antigen-positive cells in the spinal cord of Lewis rats with acute and chronic relapsing experimental autoimmune encephalomyelitis. J. Neuroimmunol. 51:153–167.

    Article  PubMed  CAS  Google Scholar 

  • McGeer, PL. and McGeer, E.G. (1995) The inflammatory response system of the brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Rev 21:195–218.

    Article  PubMed  CAS  Google Scholar 

  • McManus C., Berman, J.W., Brett, F.M., Staunton H., Farrell M., and Brosnan, C.F. (1998) MCP-1, MCP-2, and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study. J. Neuroimmunology. 86:20–29.

    Article  CAS  Google Scholar 

  • Miyagishi R., Kikuchi S., Takayama C., Inoue Y., and Tashiro, K. (1997) Identification of cell types producing RANTES, MIP-1α, and MIP-1β in rat experimental autoimmune encephalomyelitis by in situ hybridisation. J. Neuroimmunol. 77:17–26.

    Article  PubMed  CAS  Google Scholar 

  • Muhleisen H., Gehrman J., and Metermann, R. (1995) Reactive microglia in Creutzfeldt-Jakob disease. Neuropath Appl Neurophysiol 21:505–51

    Article  CAS  Google Scholar 

  • Newcombe, J. and Cuzner, M.L. (1993) Organisation and research applications of the U.K. Multiple Sclerosis Society Tissue Bank. In: How to Run a Brain Bank, F.F. Cruz-Sanchez and E. Tolosa (Eds.), J. Neural Trans. (Suppl.) 39:155–163.

    Google Scholar 

  • Noe, K.H., Fisher, S.N., Dhib-Jalbut, S.S., and Shin, M.L. (1996) Induction of cytokine RANTES by virus in astrocytes. J. Neurochem [Suppl] 66:S71D.

    Google Scholar 

  • Pan, Y, Lloyd C., Zhou H., Dolich S., Deeds J., Gonzalo, J.A., Vath J., Gosselin M., Ma, J.Y., Dussault B., Woolf E., Alperin G., Culpepper J., Gutierrez Ramos, J.C., and Gearing, D. (1997) Neurotactin, a membrane anchored chemokine upregulated in brain inflammation. Nature 387:611–617.

    Article  PubMed  CAS  Google Scholar 

  • Perry, V.H. and Gordon, S. (1991) Macrophages and the nervous system. Int Rev Cytol 125:203–244.

    Article  CAS  Google Scholar 

  • Peterson, P.K., Hu S., Salak-Johnson J., Molitor, T.W., and Chao, C.C. (1996) Differential production of and migratory response to β chemokines by human microglia and astrocytes. J Infect Dis 175:478–481.

    Article  Google Scholar 

  • Premack, B.A. and Schall, T.X (1996) Chemokine receptors: Gateway to inflammation and infection. Nature Medicine 2:1174–1178.

    Article  PubMed  CAS  Google Scholar 

  • Raine, C.S., Cannella B., Duijvestijn, A.M., and Cross, A.H. (1990) Homing to central nervous system vasculature by antigen-specific lymphocyte. 2. Lymphocyte endothelial-cell adhesion during the initial stages of autimmune demyelination. Lab. Invest. 63(4):476–489.

    PubMed  CAS  Google Scholar 

  • Ransohoff, R.M., Hamilton, T.A., Tani M., Stoler M., Shick, H.E., Major, J.A., Estes, M.L., Thomas, D.M., and Tuohy, V.K. (1993) Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental allergic encephalomyelitis. FASEB J. 7:592–600.

    PubMed  CAS  Google Scholar 

  • Ransohoff, R.M., Glabinski A., and Tani, M. (1996) Chemokines in immune-mediated inflammation of the central nervous system. Cytokine and Growth factor Reviews. 7:35–46.

    CAS  Google Scholar 

  • Schall, T.J., Bacon K., Toy, K.J., and Goeddel, D.V. (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347:669–671.

    Article  PubMed  CAS  Google Scholar 

  • Seebach J., Bartholdi D., Frei K., Spanaus, K.S., Ferrero E., Widmer U., Isenmann S., Streiter, R.M., Schwab M., and Pfister, H. (1995) Experimental Listeria meningoencephalitis. Macrophage inflammatory protein-1 (and-2 are produced intrathecally and mediate chemotactic activity in cerebrospinal fluid of infected mice. X Immunol. 155:4367–4375.

    CAS  Google Scholar 

  • Shyy, Y.J., Wickham, L.L., Hagan, J.P., Hsien, H.J., Hu, Y.L., Telian, S.H., Valente, A.J., Sung, K.L.P, and Chien, S. (1993) Human monocyte colony-stimulating factor stimulates the gene-expression of monocyte chemoattractant protein-1 and increases the adhesion of monocytes to endothelial monolayers. J. Clin. Invest. 92:1745–1751.

    Article  PubMed  CAS  Google Scholar 

  • Simpson, J.E., Newcombe J., Cuzner, M.L., and Woodroofe, M.N. (1998) Expression of monocyte chemoattractant protein-1 and other β-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol. 84:238–244.

    Article  PubMed  CAS  Google Scholar 

  • Streit, W.J. (1996) The role of microglia in brain injury. Neuro Toxicology 17:671–678.

    CAS  Google Scholar 

  • Tani, M. and Ransohoff, R.M. (1998) Do chemokines mediate inflammatory cell invasion of the central nervous system parenchyma? Brain Pathol. 4:135–143.

    Article  Google Scholar 

  • Taub, D.D. (1996) Chemokine-Leukocyte interactions. The voodoo that they do so well. Cytokine and Growth Factor Reviews 7:355–376.

    Article  PubMed  CAS  Google Scholar 

  • Vaddi K., Keller M., and Newton, R.C. (1997) The chemokine facts book. Academic press, Inc., San Diego, CA.

    Google Scholar 

  • Woodroofe, M.N., Bellamy, A.S., Feldmann M., Davison, A.N., and Cuzner, M.L. (1986) Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis-possible role for microglia in lesion growth. J Neurol Sci 74:135–152.

    Article  PubMed  CAS  Google Scholar 

  • Yao J., Harvath L., Gilbert, D.L., and Colton, C.A. (1990) Chemotaxis by a CNS macrophage, the microglia. J Neurosci Res 27:36–42.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Biomedical Research Centre, Division of Biomedical Sciences Sheffield Hallam University City Campus, Pond Street, Sheffield, South Yorkshire, S1 1WB, UK

    N. Woodroofe, A. K. Cross, K. Harkness & J. E. Simpson

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  1. N. Woodroofe
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  2. A. K. Cross
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  3. K. Harkness
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  4. J. E. Simpson
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Editors and Affiliations

  1. University of Geneva Medical School, Geneva, Switzerland

    Marco Tsacopoulos

  2. Hellenic Pasteur Institute, Athens, Greece

    Rebecca Matsas

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© 1999 Springer Science+Business Media New York

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Woodroofe, N., Cross, A.K., Harkness, K., Simpson, J.E. (1999). The Role of Chemokines in the Pathogenesis of Multiple Sclerosis. In: Matsas, R., Tsacopoulos, M. (eds) The Functional Roles of Glial Cells in Health and Disease. Advances in Experimental Medicine and Biology, vol 468. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4685-6_11

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  • DOI: https://doi.org/10.1007/978-1-4615-4685-6_11

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