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The Role of Apoptosis in Neuroinflammation

  • Conference paper
Neuroinflammation — From Bench to Bedside

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 39))

Abstract

Inflammatory diseases of the central nervous system (CNS) play a major role in clinical neurology. It is currently under debate whether inflammatory processes determine the outcome in, for example, brain injury (Woiciechowsky et al. 1998) and cerebral ischemia (Dirnagl et al. 1999). The classical and most demanding acute inflammatory disease of the CNS is bacterial meningitis which still displays a mortality rate of about 20%, despite effective antibiotic treatment (Schuchat et al. 1997). The functional outcome of bacterial meningitis regarding long-term sequelae is dictated by neuronal injury that leads to seizures, paralysis, and cognitive deficits in survivors. The most common chronic inflammatory disease of the CNS in Northern America and Europe, which causes prolonged and severe disability in young adults, is multiple sclerosis (MS). MS is thought to be an autoimmune disorder with demyelination and axonal pathology leading to clinical symptoms (Noseworthy et al. 2000). The pathogenesis in both bacterial meningitis and multiple sclerosis has not been completely elucidated, and therapies are still inefficient despite the progress made thus far. The heterogeneous clinical course of both meningitis and multiple sclerosis requires individual treatment. Since overall therapeutic options are still lacking, clinical and experimental approaches have been aimed towards identifying genes to advance pathogenetic explanation, discover predisposing parameters for various forms of the disease, and elicit suitable therapeutic strategies.

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References

  • Aktas O, Osmanova V, Beyer M, Brocke S, Zipp F (2001) Therapeutic modulation of the TRAIL system in autoimmune CNS inflammation. J Neuroimmunol 118 /1: 52

    Google Scholar 

  • Ashkenazi A, RC Pai, S Fong, S Leung, DA Lawrence, SA Marsters, C Blackie, L Chang, AE McMurtrey, A Hebert, L DeForge, IL Koumenis, D Lewis, L Harris, J Bussiere, H Koeppen, Z Shahrokh, RH Schwall (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104: 155

    Article  PubMed  CAS  Google Scholar 

  • Bachmann R, Eugster HP, Frei K, Fontana A, Lassmann H (1999) Impairment of TNF-receptor-1 signaling but not fas signaling diminishes T-cell apoptosis in myelin oligodendrocyte glycoprotein peptide-induced chronic demyelinating autoimmune encephalomyelitis in mice. Am J Pathol 154: 1417–1422

    Article  PubMed  CAS  Google Scholar 

  • Bechmann I, Mor G, Nilsen J, Eliza M, Nitsch R, Naftolin F (1999) FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: evidence for the existence of an immunological brain barrier. Glia 27: 62–74

    Article  PubMed  CAS  Google Scholar 

  • Bechmann I, Lossau S, Steiner B, Mor G, Gimsa U, Nitsch R (2000) Reactive astrocytes upregulate fas (CD95) and fas ligand (CD95L) expression but do not undergo programmed cell death during the course of anterograde degeneration. Glia 32: 25–41

    Article  PubMed  CAS  Google Scholar 

  • Bitsch A, Kuhlmann T, da Costa C, Bunkowski S, Polak T, Brück W (2000) Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: correlation with demyelinating activity and oligodendrocyte pathology. Glia 29: 366–375

    Article  PubMed  CAS  Google Scholar 

  • Boise LH, Gonzales-Garcia M, Postema CEDL, Lindsten T, Turka LA, Mao X, Nunez G, Thomson CB (1993) bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death. Cell 74: 597–608

    Google Scholar 

  • Braun JS, Tuomanen EI (1999) Molecular mechanisms of brain damage in bacterial meningitis. Adv Ped Infect Dis 14: 49–72

    CAS  Google Scholar 

  • Braun JS, Novak R, Herzog K-H, Bodner SM, Cleveland JC, Tuomanen EI (1999) Neuroprotection by a caspase inhibitor in pneumococcal meningitis. Nat Med 5: 298–302

    Article  PubMed  CAS  Google Scholar 

  • Brunner T, Mogil RJ, LaFace D, Yoo NJ, Mahboubi A, Echeverri F, Martin SJ, Force WR, Lynch DH, Ware CF, et al (1995) Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373: 441–444

    Article  PubMed  CAS  Google Scholar 

  • Chou AH, Tsai HF, Lin LL, Hsieh SL, Hsu PI, Hsu PN (2001) Enhanced proliferation and increased interferon-y production by signal transduced through TNF-related apoptosis-inducing ligand. J Immunol 167: 1347–1352

    PubMed  CAS  Google Scholar 

  • D’Souza SD, Bonetti B, Balasingam V, Cashman NR, Barker PA, Troutt AB, Raine CS, Antel JP (1996) Multiple sclerosis: Fas signaling in oligodendrocyte cell death. J Exp Med 184: 2361–2370

    Google Scholar 

  • Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG (1997a) The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7: 813–820

    Article  PubMed  CAS  Google Scholar 

  • Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang C-P, DuBose RF, Goodwin RG, Smith CA (1997b) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 186: 1165–1170

    Article  PubMed  CAS  Google Scholar 

  • Dhein J, Walczak H, Baumler C, Decatin KM, Krammer PH (1995) Autocrine T-cell suicide mediated by APO-1(Fas/CD95). Nature 373: 438–441

    Article  PubMed  CAS  Google Scholar 

  • Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22: 391–397

    Article  PubMed  CAS  Google Scholar 

  • Dittel BN, Merchant RM, Janeway CA (1999) Evidence for Fas-dependent and Fas-independent mechanisms in the pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 162: 6392–6400

    PubMed  CAS  Google Scholar 

  • Dowling P, Shang G, Raval S, Menonna J, Cook S, Husar W (1996) Involvement of the CD95 (APO-1/Fas) Receptor/Ligand System in Multiple Sclerosis Brain. J Exp Med 184: 1513–1518

    Article  PubMed  CAS  Google Scholar 

  • Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR (1998) Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 273: 14363

    Article  PubMed  CAS  Google Scholar 

  • Ferguson B, MK Matyszak, MM Esiri, VH Perry (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120: 393–390

    Article  PubMed  Google Scholar 

  • Flügel A, Schwaiger FW, Neumann H, Medana I, Willem M, Wekerle H, Kreutzberg GW, Graeber MB (2000) Neuronal FasL induces cell death of encephalitogenic T lymphocytes. Brain Pathol 10: 353–364

    Article  PubMed  Google Scholar 

  • Freyer D, Manz R, Ziegenhorn A, Weih M, Angstwurm K, Döcke WD, Meisel A, Schumann RR, Schönfelder G, Dirnagl U, Weber JR (1999) Cerebral endothelial cells release TNF-a after stimulation with cell walls of Streptococcus pneumoniae and regulate iNOS and ICAM-1 expression via autocrine loops. J Immunol 163: 4308–4314

    PubMed  CAS  Google Scholar 

  • Gniadeck P, Aktas O, Claussnitzer A, Wendling U, Obert H, Zipp F (2000) Modulation of apoptosis in MS under therapy with interferon (IFN)-131A. Rev Neurol 3S: 76

    Google Scholar 

  • Gold R, Hartung HP, Lassmann H (1997) T-cell apoptosis in autoimmune diseases: termination of inflammation in the nervous system and other sites with specialized immune-defense mechanisms. Trends Neurosci 20: 399–404

    Article  PubMed  CAS  Google Scholar 

  • Griffith TS, Herndon JM, Lima J, Kahn M, Ferguson TA (1995) The immune response and the eye. TCR alpha-chain related molecules regulate the systemic immunity to antigen presented in the eye. Int Immunol 7: 1617–1625

    Google Scholar 

  • Hilliard B, Wilmen A, Seidel C, Liu TS, Goke R, Chen Y (2001) Roles of TNF-Related Apoptosis-Inducing Ligand in Experimental Autoimmune Encephalomyelitis. J Immunol 166: 1314–1319

    PubMed  CAS  Google Scholar 

  • Hisahara S, Araki T, Sugiyama F, Yagami KI, Suzuki M, Abe K, Yamamura KI, Miyazaki JI, Momoi T, Saruta T, Bernard CC, Okano H, Miura M (2000) Targeted expression of baculovirus p35 caspase inhibitor in oligodendrocytes protects mice against autoimmune-mediated demyelination. EMBO J 19: 341–348

    Article  PubMed  CAS  Google Scholar 

  • Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bel-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334–336

    Article  PubMed  CAS  Google Scholar 

  • Hohlfeld R, E Meinl, F Weber, F Zipp, S Schmidt, S Sotgiu, N Goebels, R Voltz, S Spuler, A Iglesias, H Wekerle (1995) The role of autoimmune T lymphocytes in the pathogenesis of multiple sclerosis. Neurology 45 (56): 33–38

    Article  CAS  Google Scholar 

  • Huang W-X, Huang MP, Gomes MA, Hillert J (2000) Apoptosis mediators fasL and TRAIL are upregulated in peripheral blood mononuclear cells in MS. Neurology 55: 928–934

    Article  PubMed  CAS  Google Scholar 

  • Issazadeh S, Abdallah K, Chitnis T, Chandraker A, Wells AD, Turka LA, Sayegh MH, Khoury SJ (2000) Role of passive T-cell death in chronic experimental autoimmune encephalomyelitis. J Clin Invest 105: 1109–1116

    Article  PubMed  CAS  Google Scholar 

  • Jo M, Kim TH, Seol DW, Esplen J, Dorko K, Billiar TR, Strom SC (2000) TNF-related apoptosis inducing ligand ( TRAIL)-induced apoptosis in normal human hepatocytes. Nat Med 6: 564–567

    Google Scholar 

  • Karpus WJ, Ransohoff RM (1998) Chemokine regulation of experimental autoimmune encephalomyelitis: temporal and spatial expression patterns govern disease pathogenesis. J Immunol 161: 2667–2671

    PubMed  CAS  Google Scholar 

  • Kaser A, Deisenhammer F, Berger T, Tilg H (1999) Interferon-beta lb augments activation-induced T-cell death in multiple sclerosis patients. Lancet 353: 1413–1414

    Article  PubMed  CAS  Google Scholar 

  • Kornek B, Storch MK, Weissert R, Wallstroem E, Stefferl A, Olsson T, Linington C, Schmidbauer M, Lassmann H (2000) Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol 157: 267–276

    Article  PubMed  CAS  Google Scholar 

  • Krammer PH (1998) CD95(APO-1/Fas)-mediated apoptosis: Live and let die. Adv Immunol 71: 163–210

    Article  Google Scholar 

  • Krammer PH, Galle PR, Möller P, Debatin KM (1998) CD95 (APO-1/Fas)mediated apoptosis in normal and malignant liver, colon, and hematopoetic cells. Ernst Schering Research Foundation, Academic Press

    Google Scholar 

  • Kuhlmann T, Lucchinetti C, Zettl UK, Bitsch A, Lassmann H, Brack W (2000) Bcl-2-expressing oligodendrocytes in multiple sclerosis lesions. Glia 28: 34–39

    Article  Google Scholar 

  • Leib SL, Kim YS, Chow LL, Sheldon RA, Tauber MG (1996) Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci. J Clin Invest 98: 2632–2639

    Article  PubMed  CAS  Google Scholar 

  • Lenardo M, Chan KM, Hornung F, McFarland H, Siegel R, Wang J, Zheng L (1999) Mature T lymphocyte apoptosis-immune regulation in a dynamic and unpredictable antigenic environment. Annu Rev Immunol 17: 221–253

    Article  PubMed  CAS  Google Scholar 

  • Lenercept Multiple Sclerosis Study Group, The University of British Columbia MS/MRI Analysis Group (1999) TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. Neurology 53: 457–465

    Google Scholar 

  • Liu J, Marino MW, Wong G, Grail D, Dunn A, Bettadapura J, Slavin AJ, Old L, Bernard CC (1999) TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination. Nat Med 4: 78–83

    Article  Google Scholar 

  • Lünemann JD, Waiczies S, Wendling U, Ehrlich S, Seeger B, Kamradt T, Zipp F (2001) Death ligand TRAIL inhibits proliferation of human (auto)antigen-specific T cells without inducing apoptosis or clonal anergy. J Neuroimmunol 118 /1: 101

    Google Scholar 

  • Malipiero U, Frei K, Spanaus K-S, Agresti C, Lassmann H, Hahne M, Tschopp J, Eugster H-P, Fontana A (1997) Myelin oligodendrocyte glycoprotein-induced encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas-and Fas ligand-deficient 1pr and gld mice. Eur J Immunol 27: 3151–3160

    Article  PubMed  CAS  Google Scholar 

  • Martin R, McFarland HF, McFarlin DE (1992) Immunological aspects of demyelinating diseases. Annu Rev Immunol 10: 153–187

    Article  PubMed  CAS  Google Scholar 

  • Martino G, Hartung HP (1999) Immunopathogenesis of multiple sclerosis: the role of T cells. Curr Opin Neurol 12: 309–321

    Article  PubMed  CAS  Google Scholar 

  • Medana IM, Gallimore A, Oxenius A, Martinic MM, Wekerle H, Neumann H (2000) MHC class I-restricted killing of neurons by virus specific CD8+ T lymphocytes is effected through the Fas/FasL, but not the perforin pathway. Eur J Immunol 30: 3623–3633

    Article  PubMed  CAS  Google Scholar 

  • Meyer R, Weissert R, Diem R, Storch MK, de Graaf KL, Kramer B, Bähr M (2001) Acute neuronal apoptosis in a rat model of multiple sclerosis. J Neuroscience 21: 6214–6220

    CAS  Google Scholar 

  • Nagatani T, Okazawa H, Kambara T, Satoh K, Nishiyama T, Tokura H, Yamada R, Nakajima H (1998) Effect of natural interferon-beta on the growth of melanoma cell lines. Melanoma Res 8: 295–299

    Article  PubMed  CAS  Google Scholar 

  • Nitsch R, Bechmann I, Deisz RA, Haas DLTN, Wendling U, Zipp F (2000) Massive cell death induced by tumor-necrosis factor-related apoptosis-inducing ligand ( TRAIL) in adult human brain tissue. Lancet 356: 827–828

    Google Scholar 

  • Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple Sclerosis. New Engl J Med 343: 938–950

    Article  PubMed  CAS  Google Scholar 

  • Oltvai ZN, Milliman ZL, Korsmeyer SJ (1993) Bel-2 heterodimerizes in vivo with a conserved homolog, Box, that accelerates programmed cell death. Cell 74: 609–619

    Google Scholar 

  • Pan G, Ni J, Wei Y, Yu G, Gentz R, Dixit VM (1997a) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277: 815–818

    Article  PubMed  CAS  Google Scholar 

  • Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM (1997b) The Receptor for the Cytotoxic Ligand TRAIL. Science 276: 111–113

    Article  PubMed  CAS  Google Scholar 

  • Pender MP, Nguyen KB, McCombe PA, Kerr JF (1991) Apoptosis in the nervous system in experimental allergic encephalomyelitis. J Neurol Sci 104: 81–87

    Article  PubMed  CAS  Google Scholar 

  • Pilling D, Akbar AN, Girdlestone J, Orteu CH, Borthwick NJ, Amft, Scheel TD, Buckley CD, Salmon M (1999) Interferon-beta mediates stromal cell rescue of T cells from apoptosis. Eur J Immunol 29: 1041–1050

    Article  PubMed  CAS  Google Scholar 

  • Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271: 12687–12690

    Article  PubMed  CAS  Google Scholar 

  • Pouly S, Becher B, Blain M, Antel JP (2000) Interferon-y modulates human oligodendrocyte susceptibility to Fas-mediated apoptosis. J Neuropathol Exp Neurol 59: 280–286

    PubMed  CAS  Google Scholar 

  • Raine CS, Canella B (1992) Adhesion molecules and central nervous system inflammation. Semin Neurosci 4: 201–211

    Article  Google Scholar 

  • Reed JC (1994) Bcl-2 and the regulation of programmed cell death. J Cell Biol 124: 1–6

    Article  PubMed  CAS  Google Scholar 

  • Rep MH, Schrijver HM, van Lopik T, Hintzen RQ, Roos MT, Ader HJ, Polman CH, van Lier RA (1999) Interferon (IFN)-beta treatment enhances CD95 and interleukin 10 expression but reduces interferon-gamma producing T cells in MS patients. J Neuroimmunol 96: 92–100

    Article  PubMed  CAS  Google Scholar 

  • Roth W, Wagenknecht B, Dichgans J, Weller M (1998) Interferon-alpha enhances CD95L-induced apoptosis of human malignant glioma cells. J Neuroimmunol 87: 121–129

    Article  PubMed  Google Scholar 

  • Roth W, Isenmann S, Naumann U, Kugler S, Bahr M, Dichgans J, Ashkenazi A, Weller M (1999) Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neuro-toxicity. Biochem Bioph Res Co 265: 479

    Article  CAS  Google Scholar 

  • Sabelko KA, Kelly KA, Nahm MH, Cross AH, Russell JH (1997) Fas and Fas ligand enhance the pathogenesis of experimental allergic encephalomyelitis, but are not essential for immune privilege in the central nervous system. J Immunol 159: 3096–3099

    PubMed  CAS  Google Scholar 

  • Sabelko-Downes KA, Cross AH, Russell JH (1999) Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis. J Exp Med 189: 1195–1205

    Article  PubMed  CAS  Google Scholar 

  • Schmied M, Breitschopf H, Gold R, Zischler H, Rothe G, Wekerle H, Lass-mann H (1993) Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol 143: 446–452

    Google Scholar 

  • Schuchat A, Robinson K, Wenger JD, Harrison LH, Farley M, Reingold AL, Lefkowitz L, Perkins BA (1997) Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 337: 970–976

    Google Scholar 

  • Schumann RR, Pfeil D, Freyer D, Buerger W, Lamping N, Kirschning CJ, Goebel UB, Weber JR (1998) Lipopolysaccharide and pneumococcal cell wall components activate the mitogen activated protein kinases (MAPK) erk-1, erk-2 and p38 in astrocytes. Glia 22: 295–305

    Article  PubMed  CAS  Google Scholar 

  • Selleri C, Sato T, Del Vecchio L, Luciano L, Barrett Al, Rotoli B, Young NS, Maciejewski JP (1997) Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-a in chronic myelogenous leukemia. Blood 89: 957–964

    PubMed  CAS  Google Scholar 

  • Semra YK, Seidi OA, Sharief MK (2001) Overexpression of the apoptosis inhibitor FLIP in T cells correlates with disease activity in multiple sclerosis. J Neuroimmunol 113: 268–274

    Article  PubMed  CAS  Google Scholar 

  • Sheridan JP, Marsters S, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277: 818–821

    Article  PubMed  CAS  Google Scholar 

  • Shevach EM (2000) Regulatory T cells in autoimmunity. Annu Rev Immunol 18: 423–449

    Article  PubMed  CAS  Google Scholar 

  • Smith T, Groom A, Zhu B, Turski L (2000) Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med 6: 62–66

    Article  PubMed  CAS  Google Scholar 

  • Song K, Chen Y, Goke R, Wilmen A, Seidel C, Goke A, Hilliard B (2000) Tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL) is an inhibitor of autoimmune inflammation and cell cycle progression. J Exp Med 191: 1095–1103

    Google Scholar 

  • Suvannavejh GC, Dal Canto MC, Matis L, Miller SD (2000) Fas-mediated apoptosis in clinical remissions of relapsing experimental autoimmune encephalomyelitis. J Clin Invest 105: 223–231

    Article  PubMed  CAS  Google Scholar 

  • Sytwu HK, Liblau RS, McDevitt HO (1996) The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor trans-genic mice. Immunity 5: 17–30

    Article  PubMed  CAS  Google Scholar 

  • Tuomanen EI, Saukkonen K, Sande S, Cioffe C, Wright SD (1989) Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes. J Exp Med 170: 959–969

    Article  PubMed  CAS  Google Scholar 

  • van Oosten BW, Barkhof F, Truyen L, Boringa JB, Bertelsmann FW, von Blomberg BM, Woody JN, Hartung HP, Polman CH (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47: 1531–1534

    Article  PubMed  Google Scholar 

  • van Parijs L, Peterson DA, Abbas AK (1998) The Fas/Fas ligand pathway and bc1–2 regulate T cell responses to model self and foreign antigens Immunity 8: 265–274

    Google Scholar 

  • Walczak H, Degli Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin R, Rauch CT (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16: 5386–5397

    Article  PubMed  CAS  Google Scholar 

  • Walczak, H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5: 157

    Article  PubMed  CAS  Google Scholar 

  • Waldner H, Sobel RA, Howard E, Kuchroo VK (1997) Fas-and FasL-deficient mice are resistant to induction of autoimmune encephalomyelitis J Immunol 159: 3100–3103

    CAS  Google Scholar 

  • Weber F, Meinl E, Aloisi F, Nevinny-Stickel C, Albert E, Wekerle H, Hohlfeld R (1994) Human astrocytes are only partially competent antigen presenting cells. Possible implications for lesion development in multiple sclerosis. Brain 117: 1323–1332

    Google Scholar 

  • Wekerle H, Kojima K, Lannes-Vieira J, Lassmann H, Linington C (1994) Animal models. Ann Neurol 36: S47–53

    Article  CAS  Google Scholar 

  • Wendling U, Walczak H, Dörr J, Jaboci C, Weller M, Krammer PH, Zipp F (2000) Expression of TRAIL receptors in human autoreactive and foreign antigen-specific T cells. Cell Death Differ 7: 637–644

    Article  PubMed  CAS  Google Scholar 

  • Wildbaum G, Westermann J, Maor G, Karin N (2000) A targeted DNA vaccine encoding fas ligand defines its dual role in the regulation of experimental autoimmune encephalomyelitis. J Clin Invest 106: 671–679

    Article  PubMed  CAS  Google Scholar 

  • Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, Goodwin RG (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3: 673–682

    Article  Google Scholar 

  • Williams K, Ulvestad E, Antel JP (1994) B7/BB-1 antigen expression on adult human microglia studied in vitro and in situ. Eur J Immunol 24: 3031–3037

    Article  PubMed  CAS  Google Scholar 

  • Woiciechowsky C, Asadullah K, Nestler D, Eberhardt B, Platzer C, Schoning B, Glockner F, Lanksch WR, Volk HD, Docke WD (1998) Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med 4: 808–813

    Article  PubMed  CAS  Google Scholar 

  • Yang E, Korsmeyer SJ (1996) Molecular thanatopsis: a discourse on the bc1–2 family and cell death. Blood 88: 386–401

    PubMed  CAS  Google Scholar 

  • Zang YC, Kozovska MM, Hong J, Li S, Mann S, Killian JM, Rivera VM, Zhang JZ (1999) Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis. Eur J Immunol 29: 1692–1700

    Article  PubMed  CAS  Google Scholar 

  • Zipp F, Otzelberger K, Dichgans J, Martin R, Weller M (1998a) Serum CD95 of multiple sclerosis patients protects from CD95-mediated apoptosis. J Neuroimmunol 86: 151–154

    Article  PubMed  CAS  Google Scholar 

  • Zipp F, Weller M, Calabresi PA, Frank JA, Bash CN, Dichgans J, McFarland H, Martin R (1998b) Increased serum levels of soluble CD95 (APO1/Fas) in relapsing remitting multiple sclerosis. Ann Neurol 43: 116–120

    Article  PubMed  CAS  Google Scholar 

  • Zipp F, Krammer PH, Weller M (1999) Immune (dys)regulation in multiple sclerosis: role of the CD95/CD95 ligand system. Immunol Today 20: 550–554

    Article  PubMed  CAS  Google Scholar 

  • Zipp F, Beyer M, Gelderblom H, Wernet D, Zschenderlein R, Weller M (2000a) No induction of apoptosis by IFN-13 in human. Neurology 54: 524–526

    Article  Google Scholar 

  • Zipp F, Wendling U, Beyer M, Grieger U, Waiczies S, Wagenknecht B, Haas J, Weller M (2000b) Dual effect of glucocorticoids on apoptosis of human autoreactive and foreign antigen-specific T cells. J Neuroimmunol 110: 214

    Article  PubMed  CAS  Google Scholar 

  • Zysk G, Bruck W, Gerber J, Bruck Y, Prange HW, Nau R (1996) Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyms in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 55: 722–728

    Article  PubMed  CAS  Google Scholar 

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Zipp, F., Aktas, O., Lünemann, J.D. (2002). The Role of Apoptosis in Neuroinflammation. In: Kettenmann, H., Burton, G.A., Moenning, U.J. (eds) Neuroinflammation — From Bench to Bedside. Ernst Schering Research Foundation Workshop, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-05073-6_12

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