title: Neuromelanin is an immune stimulator for dendritic cells in vitro.
abstract: BACKGROUND
  Parkinson's disease (PD) is characterized at the cellular level by a destruction of neuromelanin (NM)-containing dopaminergic cells and a profound reduction in striatal dopamine. It has been shown recently that anti-melanin antibodies are increased in sera of Parkinson patients, suggesting that NM may act as an autoantigen. In this study we tested whether NM is being recognized by dendritic cells (DCs), the major cell type for inducing T- and B-cell responses in vivo. This recognition of NM by DCs is a prerequisite to trigger an adaptive autoimmune response directed against NM-associated structures.
  
  
  RESULTS
  Murine DCs were treated with NM of substantia nigra (SN) from human subjects or with synthetic dopamine melanin (DAM). DCs effectively phagocytized NM and subsequently developed a mature phenotype (CD86(high)/MHCII(high)). NM-activated DCs secreted the proinflammatory cytokines IL-6 and TNF-α. In addition, they potently triggered T cell proliferation in a mixed lymphocyte reaction, showing that DC activation was functional to induce a primary T cell response. In contrast, DAM, which lacks the protein and lipid components of NM but mimics the dopamine-melanin backbone of NM, had only very little effect on DC phenotype and function.
  
  
  CONCLUSIONS
  NM is recognized by DCs in vitro and triggers their maturation. If operative in vivo, this would allow the DC-mediated transport and presentation of SN antigens to the adaptive immune system, leading to autoimmmunity in susceptible individuals. Our data provide a rationale for an autoimmune-based pathomechanism of PD with NM as the initial trigger.
authors.affiliation: University of Würzburg, Institute of Virology and Immunobiology, Würzburg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Oberländer
authors.forename: Katrien
authors.initials: K
authors.lastname: Pletinckx
authors.forename: Anja
authors.initials: A
authors.lastname: Döhler
authors.forename: Nora
authors.initials: N
authors.lastname: Müller
authors.forename: Manfred B
authors.initials: MB
authors.lastname: Lutz
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Manfred
authors.initials: M
authors.lastname: Gerlach
authors.forename: Eleni
authors.initials: E
authors.lastname: Koutsilieri
authors.forename: Carsten
authors.initials: C
authors.lastname: Scheller
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D008543:Melanins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000276:immunology* / Q000473:pathology*
chemical_list: D008543:Melanins; C014121:neuromelanin
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