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CD200–CD200R Regulation of Microglia Activation in the Pathogenesis of Parkinson’s Disease

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Abstract

The role of CD200–CD200R signaling in immune regulation of the central nervous system has become a popular field of research in recent years. Many studies have shown that there is a close correlation between CD200–CD200R, microglia activation, and Parkinson’s disease (PD). This review discusses the above relationship, highlighting (1) the gene mapping and molecular structure of CD200 and CD200R, (2) the distribution and expression of CD200 and CD200R in the nervous system, (3) the effect of CD200–CD200R signaling on microglia activation, and (4) the role of microglia activation in the pathogenesis and progression of PD. Finally, we discuss the status of current studies on the regulation of microglia activation in PD and strongly suggest that it is very promising to regulate microglia activation in PD via targeting CD200–CD200R signaling pathways.

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References

  • Arimoto T, Choi DY, Lu X, Liu M, Nguyen XV, Zheng N, Stewart CA, Kim HC, Bing G (2006) Interleukin-10 protects against inflammation-mediated degeneration of dopaminergic neurons in substantia nigra. Neurobiol Aging (in press)

  • Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE (2003) A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci 23:2665–2674

    PubMed  CAS  Google Scholar 

  • Banerjee D, Dick AD (2004) Blocking CD200–CD200 receptor axis augments NOS-2 expression and aggravates experimental autoimmune uveoretinitis in Lewis rats. Ocul Immunol Inflamm 12:115–125

    Article  PubMed  CAS  Google Scholar 

  • Barclay AN (1981) Different reticular elements in rat lymphoid tissue identified by localization of Ia, Thy-1 and MRC OX 2 antigens. Immunology 44:727–736

    PubMed  CAS  Google Scholar 

  • Barclay AN, Ward HA (1982) Purification and chemical characterisation of membrane glycoproteins from rat thymocytes and brain, recognised by monoclonal antibody MRC OX 2. Eur J Biochem 129:447–458

    Article  PubMed  CAS  Google Scholar 

  • Bartolome MV, Ibanez-Olias MA, Gil-Loyzaga P (2002) Transitional expression of OX-2 and GAP-43 glycoproteins in developing rat cochlear nerve fibers. Histol Histopathol 17:83–95

    PubMed  CAS  Google Scholar 

  • Basu A, Krady JK, Enterline JR, Levison SW (2002) Transforming growth factor beta1 prevents IL-1beta-induced microglial activation, whereas TNFalpha- and IL-6-stimulated activation are not antagonized. Glia 40:109–120

    Article  PubMed  Google Scholar 

  • Berman ME, Muller WA (1995) Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18). J Immunol 154:299–307

    PubMed  CAS  Google Scholar 

  • Block ML, Hong JS (2005) Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol 76:77–98

    Article  PubMed  CAS  Google Scholar 

  • Broderick C, Hoek RM, Forrester JV, Liversidge J, Sedgwick JD, Dick AD (2002) Constitutive retinal CD200 expression regulates resident microglia and activation state of inflammatory cells during experimental autoimmune uveoretinitis. Am J Pathol 161:1669–1677

    PubMed  CAS  Google Scholar 

  • Bukovsky A, Presl J, Zidovsky J, Mancal P (1983) The localization of Thy-1.1, MRC OX 2 and Ia antigens in the rat ovary and fallopian tube. Immunology 48:587–596

    PubMed  CAS  Google Scholar 

  • Chen S, Le WD, Xie WJ, Alexianu ME, Engelhardt JI, Siklos L, Appel SH (1998) Experimental destruction of substantia nigra initiated by Parkinson disease immunoglobulins. Arch Neurol 55:1075–1080

    Article  PubMed  CAS  Google Scholar 

  • Deckert M, Sedgwick JD, Fischer E, Schluter D (2006) Regulation of microglial cell responses in murine toxoplasma encephalitis by CD200/CD200 receptor interaction. Acta Neuropathol (Berl) 111:548–558

    Article  Google Scholar 

  • Delgado M, Ganea D (2003) Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson’s disease by blocking microglial activation. FASEB J 17:944–946

    PubMed  CAS  Google Scholar 

  • Di Monte DA (2003) The environment and Parkinson’s disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol 2:531–538

    Article  PubMed  Google Scholar 

  • Frank MG, Barrientos RM, Biedenkapp JC, Rudy JW, Watkins LR, Maier SF (2006) mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging. Neurobiol Aging 27:717–722

    Article  PubMed  CAS  Google Scholar 

  • Gao HM, Hong JS, Zhang W, Liu B (2002a) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22:782–790

    PubMed  CAS  Google Scholar 

  • Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B (2002b) Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem 81:1285–1297

    Article  PubMed  CAS  Google Scholar 

  • Gao HM, Hong JS, Zhang W, Liu B (2003a) Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson’s disease. J Neurosci 23:1228–1236

    PubMed  CAS  Google Scholar 

  • Gao HM, Liu B, Zhang W, Hong JS (2003b) Synergistic dopaminergic neurotoxicity of MPTP and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson’s disease. FASEB J 17:1957–1959

    PubMed  CAS  Google Scholar 

  • Gao HM, Liu B, Zhang W, Hong JS (2003c) Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J 17:1954–1956

    PubMed  CAS  Google Scholar 

  • Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006) In vivo imaging of microglial activation with ((11)C)(R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21:404–412

    Article  PubMed  CAS  Google Scholar 

  • Gorczynski RM, Chen Z, Clark DA, Kai Y, Lee L, Nachman J, Wong S, Marsden P (2004a) Structural and functional heterogeneity in the CD200R family of immunoregulatory molecules and their expression at the feto-maternal interface. Am J Reprod Immunol 52:147–163

    Article  PubMed  Google Scholar 

  • Gorczynski R, Chen Z, Kai Y, Lee L, Wong S, Marsden PA (2004b) CD200 is a ligand for all members of the CD200R family of immunoregulatory molecules. J Immunol 172:7744–7749

    PubMed  CAS  Google Scholar 

  • Gorczynski RM (2005) CD200 and its receptors as targets for immunoregulation. Curr Opin Investig Drugs 6:483–488

    PubMed  CAS  Google Scholar 

  • Hatherley D, Barclay AN (2004) The CD200 and CD200 receptor cell surface proteins interact through their N-terminal immunoglobulin-like domains. Eur J Immunol 34:1688–1694

    Article  PubMed  CAS  Google Scholar 

  • He Y, Appel S, Le W (2001) Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res 909:187–193

    Article  PubMed  CAS  Google Scholar 

  • Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, Barclay AN, Sedgwick JD (2000) Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290:1768–1771

    Article  PubMed  CAS  Google Scholar 

  • Ilan N, Madri JA (2003) PECAM-1: old friend, new partners. Curr Opin Cell Biol 15:515–524

    Article  PubMed  CAS  Google Scholar 

  • Jenmalm MC, Cherwinski H, Bowman EP, Phillips JH, Sedgwick JD (2006) Regulation of myeloid cell function through the CD200 receptor. J Immunol 176:191–199

    PubMed  CAS  Google Scholar 

  • Jones LL, Kreutzberg GW, Raivich G (1998) Transforming growth factor beta’s 1, 2 and 3 inhibit proliferation of ramified microglia on an astrocyte monolayer. Brain Res 795:301–306

    Article  PubMed  CAS  Google Scholar 

  • Kim YS, Joh TH (2004) Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson’s disease. Exp Mol Med 38:333–347

    Google Scholar 

  • Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS (2000) Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci 20:6309–6316

    PubMed  CAS  Google Scholar 

  • Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39:151–170

    Article  PubMed  CAS  Google Scholar 

  • Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH (2001) Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson’s disease. J Neurosci 21:8447–8855

    PubMed  CAS  Google Scholar 

  • Li R, Huang YG, Fang D, Le WD (2004) (−)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res 78:723–731

    Article  PubMed  CAS  Google Scholar 

  • Liu B, Du L, Hong JS (2000a) Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther 293:607–617

    CAS  Google Scholar 

  • Liu B, Jiang JW, Wilson B, Du L, Yang SN, Wang JY, Wu GC, Cao XD, Hong JS (2000b) Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 295:125–132

    CAS  Google Scholar 

  • Liu B, Gao HM, Hong JS (2003a) Parkinson’s disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation. Environ Health Perspect 111:1065–1073

    CAS  Google Scholar 

  • Liu B, Hong JS (2003b) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7

    Article  CAS  Google Scholar 

  • Liu Y, Qin L, Li G, Zhang W, An L, Liu B, Hong JS (2003c) Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. J Pharmacol Exp Ther 305:212–218

    Article  CAS  Google Scholar 

  • Lu X, Bing G, Hagg T (2000) Naloxone prevents microglia-induced degeneration of dopaminergic substantia nigra neurons in adult rats. Neuroscience 97:285–291

    Article  PubMed  CAS  Google Scholar 

  • Morris RJ, Beech JN (1987) Sequential expression of OX2 and Thy-1 glycoproteins on the neuronal surface during development. An immunohistochemical study of rat cerebellum. Dev Neurosci 9:33–44

    PubMed  CAS  Google Scholar 

  • Nathan C, Muller WA (2001) Putting the brakes on innate immunity: a regulatory role for CD200? Nat Immunol 2:17–19

    Article  PubMed  CAS  Google Scholar 

  • Newman PJ (1997) The biology of PECAM-1. J Clin Invest 99:3–8

    Article  PubMed  CAS  Google Scholar 

  • Orth M, Tabrizi SJ (2003) Models of Parkinson’s disease. Mov Disord 18:729–737

    Article  PubMed  Google Scholar 

  • Purisai MG, McCormack AL, Cumine S, Li J, Isla MZ, Di Monte DA (2007) Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiol Dis 25:392–400

    Article  PubMed  CAS  Google Scholar 

  • Qian L, Block ML, Wei SJ, Lin CF, Reece J, Pang H, Wilson B, Hong JS, Flood PM (2006) Interleukin-10 protects lipopolysaccharide-induced neurotoxicity in primary midbrain cultures by inhibiting the function of NADPH oxidase. J Pharmacol Exp Ther 319:44–52

    Article  PubMed  CAS  Google Scholar 

  • Siglienti I, Chan A, Kleinschnitz C, Jander S, Toyka KV, Gold R, Stoll G (2007) Downregulation of transforming growth factor-beta2 facilitates inflammation in the central nervous system by reciprocal astrocyte/microglia interactions. J Neuropathol Exp Neurol 66:47–56

    PubMed  CAS  Google Scholar 

  • Sugama S, Yang L, Cho BP, DeGiorgio LA, Lorenzl S, Albers DS, Beal MF, Volpe BT, Joh TH (2003) Age-related microglial activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration in C57BL/6 mice. Brain Res 964:288–294

    Article  PubMed  CAS  Google Scholar 

  • Vieites JM, de la Torre R, Ortega MA, Montero T, Peco JM, Sanchez-Pozo A, Gil A, Suarez A (2003) Characterization of human cd200 glycoprotein receptor gene located on chromosome 3q12–13. Gene 311:99–104

    Article  PubMed  CAS  Google Scholar 

  • Wang XJ, Chen SD, Ma GZ, Ye M, Lu GX (2005a) Genistein protects dopaminergic neurons by inhibiting microglial activation. Neuroreport 16:267–270

    Article  PubMed  CAS  Google Scholar 

  • Wang XJ, Chen SD, Ma GZ, Ye M, Lu GZ (2005b) Involvement of proinflammatory factors, apoptosis, caspase-3 activation and Ca2+ disturbance in microglia activation-mediated dopaminergic cell degeneration. Mech Ageing Dev 126:1241–1254

    Article  PubMed  CAS  Google Scholar 

  • Wang XJ, Yan ZQ, Lu GQ, Stuart S, Chen SD (2007) Parkinson disease IgG and C5a-induced synergistic dopaminergic neurotoxicity: role of microglia. Neurochem Int 50:39–50

    Article  PubMed  CAS  Google Scholar 

  • Webb M, Barclay AN (1984) Localisation of the MRC OX-2 glycoprotein on the surfaces of neurones. J Neurochem 43:1061–1067

    Article  PubMed  CAS  Google Scholar 

  • Wojtera M, Sikorska B, Sobow T, Liberski PP (2005) Microglial cells in neurodegenerative disorders. Folia Neuropathol 43:311–321

    PubMed  CAS  Google Scholar 

  • Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, Barclay AN (2000) Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity 13:233–242

    Article  PubMed  CAS  Google Scholar 

  • Wright GJ, Jones M, Puklavec MJ, Brown MH, Barclay AN (2001) The unusual distribution of the rat lymphoid/neuronal OX2 glycoprotein is conserved in humans (CD200). Immunology 102:173–179

    Article  PubMed  CAS  Google Scholar 

  • Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ, Bigler M, Song Y, Jenmalm M, Gorman D, McClanahan T, Liu MR, Brown MH, Edgwick JD, Phillips JH, Barclay AN (2003) Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J Immunol 171:3034–3046

    PubMed  CAS  Google Scholar 

  • Zhang S, Cherwinski H, Sedgwick JD, Phillips JH (2004) Molecular mechanisms of CD200 inhibition of mast cell activation. J Immunol 173:6786–6793

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was granted by the National Program of Basic Research (2006cb500706) of China, the National Natural Science Fund (30570637, 30471918), Shanghai Key Project of Basic Science Research (04DZ14005), and Program for Outstanding Medical Academic Leader (LJ 06003).

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Authors and Affiliations

  1. Department of Neurology & Institute of Neurology, Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Xi-Jin Wang, Min Ye, Yu-Hong Zhang & Sheng-Di Chen

  2. Lab of Neurodegenerative Diseases, Institute of Health Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Science and Shanghai Jiaotong University School of Medicine, Shanghai, 200025, People’s Republic of China

    Sheng-Di Chen

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  1. Xi-Jin Wang
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  2. Min Ye
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  3. Yu-Hong Zhang
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  4. Sheng-Di Chen
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Correspondence to Sheng-Di Chen.

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Wang, XJ., Ye, M., Zhang, YH. et al. CD200–CD200R Regulation of Microglia Activation in the Pathogenesis of Parkinson’s Disease. Jrnl Neuroimmune Pharm 2, 259–264 (2007). https://doi.org/10.1007/s11481-007-9075-1

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  • DOI: https://doi.org/10.1007/s11481-007-9075-1

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