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Free Radicals and Experimental Autoimmune Encephalomyelitis

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Experimental Models of Multiple Sclerosis

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Abstract

This chapter reviews the major reactive oxygen and nitrogen species, their generation and their relevance for EAE. The relative contribution of NO and ONOO- species is discussed and the current literature EAE reviewed. The dual nature of free radicals, pathogenic and protective, and the correspondingly conflicting results of therapeutic interventions aimed at diminishing free radicals (in particular reactive nitrogen species), are also discussed in this chapter.

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References

  1. Kolb H, Kolb-Bachofen V (1998) NO in autoimmune disease: cytotoxic or regulatory mediator? Immunol Today 19, 556–561

    Article  PubMed  CAS  Google Scholar 

  2. Merrill JE, Scolding NJ (1999) Mechanism of damage to myelin and oligodendrocytes and their relevance to disease. Neuropathol App Neurobiol 2, 435–458

    Article  Google Scholar 

  3. Smith KJ, Kapoor R, Felts PA (1999) Demyelination: The role of reactive oxygen and nitrogen species. Brain Pathol 9, 69–92

    Article  PubMed  CAS  Google Scholar 

  4. Willenborg DO, Staykova MA, Cowden WB (1999) Our shifting understanding of the role of nitric oxide in autoimmune encephalomyelitis. J Neuroimmunol 100: 21–35

    Article  PubMed  CAS  Google Scholar 

  5. Alderton WK, Cooper CE, Knowles RG (2001) NO synthase: structure, function and inhibition. Biochem J 357, 593–615

    Article  PubMed  CAS  Google Scholar 

  6. Forstermann U, Boissel J-P, Kleinert H (1998) Expressional control of the constitutive isoforms of nitric oxide synthase. FASEB J. 12, 773–790.

    PubMed  CAS  Google Scholar 

  7. Murphy S (2000) Production of nitric oxide by glial cells. Glia 29, 1–14

    Article  PubMed  CAS  Google Scholar 

  8. Nathan C, Shiloh MU (2000) Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci USA 97, 8841–8848

    Article  PubMed  CAS  Google Scholar 

  9. Liu J, Zhao M-L, Brosnan CF, Lee SC (2001) Expression of inducible NO synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol 158, 2057–2066

    PubMed  CAS  Google Scholar 

  10. Calabrese V, Scapagnini G, Ravagna A, Bella R, Foresti R, Bates TE, Giuffrida Stella A-M, Pennisi G (2002) NO synthase is present in the CSF of patients with active MS and is associated with increases in CSF protein nitrotyrosine and S-nitrosothiols with changes in glutathione levels. J Neurosci Res 70, 580–587

    Article  PubMed  CAS  Google Scholar 

  11. Boullerne AI, Rodriguez JJ, Touil T, Brochet B, Schmidt S, Abrous ND, Le Moal M, Pua JR, Jensen MA, Mayo W, Arnason BG, Petry KG (2002) Anti-S-nitrosocysteine antibodies are a predictive marker for demyelination in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neurosci 22: 123–132

    PubMed  CAS  Google Scholar 

  12. Modin H, Dai Y, Masterman T, Svejgaard A, Sorensen PS, Oturai A, Ryder LP, Spurkland A, Vartdal F, Laaksonen M, Sandberg-Wollheom M, Myhr KM, Nyland H, Hillert J (2001) No linkage or association of the NO synthase genes to multiple sclerosis. J Neuroimmunol 119, 95–100

    Article  PubMed  CAS  Google Scholar 

  13. Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J. Cerebral Blood Flow Metab. 21, 2–14

    Article  CAS  Google Scholar 

  14. Davis KL, Martin E, Turko IV, Murad F (2001) Novel effects of nitric oxide Annu. Rev. Pharmacol. Toxicol. 41: 203–236.

    Article  CAS  Google Scholar 

  15. Stuehr D, Pou S, Rosen GM (2001) Oxygen reduction by NO synthase. J Biol Chem, 276, 14533–14536

    Article  PubMed  CAS  Google Scholar 

  16. MacMicking JD, Willenborg DO, Weidemann MJ, Rockett KA, Cowden WB (1992) Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute EAE. J Exp Med 176, 303–307

    Article  PubMed  CAS  Google Scholar 

  17. Pfeiffer A, Lass A, Schmidt K, Mayer B (2001) Protein tyrosine nitration in cytokine-activated murine macrophages — involvement of a peroxidase/nitrite pathway rather than peroxynitrite. J Biol Chem 276, 34051–34058

    Article  PubMed  CAS  Google Scholar 

  18. Zielasek J, Jung S, Gols R, Liew FY, Toyka KV, Hartung HP (1995) Administration of nitric oxide inhibitors in experimental autoimmune neuritis and EAE. J Neuroimmunol 58,81–88

    Article  PubMed  CAS  Google Scholar 

  19. Okuda Y, Sakoda S, Fujimura H, Yanagihara T (1997) Nitric oxide via an inducible isoform of NOS is a possible factor to eliminate inflammatory cells from the CNS of mice with EAE. J Neuroimmunol 73, 107–116

    Article  PubMed  CAS  Google Scholar 

  20. Martinez I, Puerta C, Redondo C, Garcia_Merino A (1999) Type IV phosphodiesterase inhibition in experimental allergic encephalomyelitis of Lewis rats: sequential gene expression analysis of cytokines, adhesion molecules and the inducible nitric oxide synthase. J Neurol Sci 164, 13–23

    Article  PubMed  CAS  Google Scholar 

  21. Gold DP, Schroder K, Powell HC, Kelly CJ (1997) Nitric oxide and the immunomodulation of EAE. Europ J Immunol 27, 2863–2869

    Article  CAS  Google Scholar 

  22. Hooper DC, Scott GS, Zborek A, Mikheeva T, Kean RB, Koprowski H, Spitsin SV (2000) Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis. FASEB J 14, 691–698

    PubMed  CAS  Google Scholar 

  23. Kean RB, Spitsin SV, Mikheeva T, Scott GS, Hooper DC (2000) The peroxynitrite scavenger uric acid prevents inflammatory cell invasion into the CNS in EAE through maintenance of blood-CNS barrier integrity. J Immunol 165, 6511–6518

    PubMed  CAS  Google Scholar 

  24. Spitsin SV, Scott GS, Kean RB, Mikheeva T, Hooper DC (2000) Protection of myelin basic protein immunized mice from free-radical mediated inflammatory cell invasion of the central nervous system by the natural peroxynitrite scavenger uric acid. Neurosci Lett 292, 137–41

    Article  PubMed  CAS  Google Scholar 

  25. Scott GS, Kean RB, Southan GJ, Szabo C, Hooper DC (2001) Effect of mercaptoethylguanidine scavengers of peroxynitrite on the development of experimental allergic encephalomyelitis in PLSJL mice. Neurosci Lett 311, 125–128

    Article  PubMed  CAS  Google Scholar 

  26. Spitsin SV, Scott GS, Mikheeva T, Zborek A, Kean RB, Brimer CM, Koprowsi H, Hooper DC (2002) Comparison of uric acid and ascorbic acid in protection against EAE. Free Rad Biol Med 33, 1363–1371

    Article  PubMed  CAS  Google Scholar 

  27. Hooper DC, Spitsin SV, Kean RB, Champion JM, Dickson GM, Chaudhry I, Koprowsi H, (1998) Uric acid, a natural scavenger of peroxynitrite, in EAE and MS. Proc Natl Acad Sci USA 95, 675–680

    Article  PubMed  CAS  Google Scholar 

  28. Cross AH, San M, Stern MK, Keeling RM, Salvemini D, Misko TP (2000) A catalyst of peroxynitrite decomposition inhibits murine experimental autoimmune encephalomyelitis. J Neuroimmunol 107, 21–28

    Article  PubMed  CAS  Google Scholar 

  29. Scott GS, Bolton C (2000) L-arginine modifies free radical production and the development of experimental allergic encephalomyelitis. Inflamm Res 49, 720–726

    Article  PubMed  CAS  Google Scholar 

  30. Staykova MA, Cowden W, Willenborg DO (2002) Macrophages and nitric oxide as the possible cellular and molecular basis for strain and gender differences in susceptibility to autoimmune central nervous system inflammation. Immunol Cell Biol 80, 188–197

    Article  PubMed  CAS  Google Scholar 

  31. Marchetti B, Morale MC, Brouwer J, Tirolo C, Testa N, Caniglia S, Barden N, Amor S, Smith PA, Dijkstra CD (2002) Exposure to a dysfunctional glucocorticoid receptor from early embryonic life programs the resistance to experimental autoimmune encephalomyelitis via nitric oxide-induced immunosuppression. J Immunol 16, 5848–5859

    Google Scholar 

  32. Xu L, Huang Y, Yang J, Van Der Meide PH, Levi M, Wahren B, Link H, Xiao B (1999) Dendritic cell-derived nitric oxide is involved in IL-4-induced suppression of experimental allergic encephalomyelitis (EAE) in Lewis rats. Clin Exp Immunol 118, 115–121

    Article  PubMed  CAS  Google Scholar 

  33. Xu LY, Yang JS, Link H, Xiao BG (2001) SIN-1, a nitric oxide donor, ameliorates experimental allergic encephalomyelitis in Lewis rats in the incipient phase: the importance of the time window. J Immunol 166: 5810–5816

    PubMed  CAS  Google Scholar 

  34. Weishaupt A, Jander S, Brack W, Kuhlmann T, Stienekemeier M, Hartung T, Toyka KV, Stoll G, Gold R (2000) Molecular mechanisms of high-dose antigen therapy in experimental autoimmune encephalomyelitis: rapid induction of Th1-type cytokines and inducible nitric oxide synthase. J Immunol 165, 7157–7163

    PubMed  CAS  Google Scholar 

  35. Kuschnaroff LM, Overbergh L, Sefriouni H, Sobis H, Vandeputte M, Waer M (1999) Effect of staphylococcal enterotoxin B injection on the development of experimental autoimmune encephalomyelitis: influence of cytokine and inducible nitric oxide synthase production. J Neuroimmunol 99, 157–168

    Article  PubMed  CAS  Google Scholar 

  36. Kahn DA, Archer DC, Gold DP, Kelly CJ (2001) Adjuvant immunotherapy is dependent on inducible nitric oxide synthase. J Exp Med 193, 1261–8

    Article  PubMed  CAS  Google Scholar 

  37. Ahn M, Kang J, Lee Y, Riu K, Kim Y, Jee Y, Matsumoto Y, Shin T (2001) Pertussis toxin-induced hyperacute autoimmune encephalomyelitis in Lewis rats is correlated with increased expression of inducible nitric oxide synthase and tumor necrosis factor alpha. Neurosci Lett 308, 41–44

    Article  PubMed  CAS  Google Scholar 

  38. Pozza M, Bettelli C, Aloe L, Giardino L, Calza L (2000) Further evidence for a role of nitric oxide in experimental allergic encephalomyelitis: aminoguanidine treatment modifies its clinical evolution. Brain Res 855, 39–46

    Article  PubMed  CAS  Google Scholar 

  39. Murphy P, Sharp A, Shin J, Gavrilyuk V, Dello Russo C, Weinberg G, Sharp FR, Lu A, Heneka MT, Feinstein DL (2002) Suppressive effects of ansamycins on inducible nitric oxide synthase expression and the development of experimental autoimmune encephalomyelitis. J Neurosci Res 67, 461–470

    Article  PubMed  CAS  Google Scholar 

  40. O_Brien NC, Charlton B, Cowden WB, Willenborg DO (2001) Inhibition of nitric oxide synthase initiates relapsing remitting experimental autoimmune encephalomyelitis in rats, yet nitric oxide appears to be essential for clinical expression of disease. J Immunol 167, 5904–5912

    PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Institute of Cell Signalling, Medical School, QMC, University of Nottingham, UK

    Sean Murphy

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  1. Sean Murphy
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Editor information

Editors and Affiliations

  1. Weill Medical College of Cornell University, New York

    Ehud Lavi

  2. Queen’s Medical Centre, University Hospital, Nottingham, UK

    Cris S. Constantinescu

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© 2005 Springer Science+Business Media, Inc.

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Murphy, S. (2005). Free Radicals and Experimental Autoimmune Encephalomyelitis. In: Lavi, E., Constantinescu, C.S. (eds) Experimental Models of Multiple Sclerosis. Springer, Boston, MA. https://doi.org/10.1007/0-387-25518-4_18

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