title: Expression of activity-dependent neuroprotective protein in the immune system: possible functions and relevance to multiple sclerosis.
abstract: BACKGROUND
  Activity-dependent neuroprotector (ADNP) is a neuroprotective molecule containing an 8-amino acid peptide, NAPVSIPQ (NAP), that is sufficient for its neuroprotective effects.
  
  
  OBJECTIVE
  To assess the expression of ADNP in the human immune system in normal subjects and multiple sclerosis patients. MaterialsandMethods: ADNP expression was assessed in peripheral blood mononuclear cells (PBMCs) from healthy donors and multiple sclerosis (MS) patients using staining with anti-ADNP (NAP) antibodies and markers for T cells, B cells, monocytes and natural killer cells. ADNP mRNA was determined in peripheral blood from MS patients (n = 24) and matched controls (n = 21). Expression of activation markers CD69 and CD154 and of IFN-gamma was assessed by flow cytometry in stimulated PBMCs. Effects of NAP on immune cell proliferation was assessed by tritiated thymidine incorporation.
  
  
  RESULTS
  Monocytes, B cells and T cells, but not regulatory (CD4+CD25+) T cells expressed ADNP. NAP peptide decreased the expression of CD69, CD154 and IFN-gamma in PBMC and caused suppressed anti-CD3-/anti-CD28-stimulated PBMC proliferation. ADNP mRNA was reduced in MS compared to control peripheral blood.
  
  
  CONCLUSIONS
  ADNP is expressed in many immune system cells. ADNP mRNA is reduced in PBMCs in MS. The peptide NAP, which plays an important role in neuroprotection, has potential immunomodulatory properties.
authors.affiliation: Division of Clinical Neurology, School of Clinical Sciences, Nottingham University, Nottingham, UK.
authors.forename: Manjit
authors.initials: M
authors.lastname: Braitch
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Kawabe
authors.forename: Mukanthu
authors.initials: M
authors.lastname: Nyirenda
authors.forename: Lucie Jean
authors.initials: LJ
authors.lastname: Gilles
authors.forename: R Adrian
authors.initials: RA
authors.lastname: Robins
authors.forename: Bruno
authors.initials: B
authors.lastname: Gran
authors.forename: Sean
authors.initials: S
authors.lastname: Murphy
authors.forename: Louise
authors.initials: L
authors.lastname: Showe
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
mesh_terms: D000954:Antigens, Surface / Q000032:analysis / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism*; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000502:physiology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: C492178:ADNP protein, human; D000954:Antigens, Surface; D015415:Biomarkers; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D012333:RNA, Messenger; C425904:davunetide