Expression of activity-dependent neuroprotective protein in the immune system: possible functions and relevance to multiple sclerosis.
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.
Braitch
Manjit
M
Division of Clinical Neurology, School of Clinical Sciences, Nottingham University, Nottingham, UK.
Kawabe
Kiyokazu
K
Nyirenda
Mukanthu
M
Gilles
Lucie Jean
LJ
Robins
R Adrian
RA
Gran
Bruno
B
Murphy
Sean
S
Showe
Louise
L
Constantinescu
Cris S
CS
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
C492178:ADNP protein, human; D000954:Antigens, Surface; D015415:Biomarkers; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; D012333:RNA, Messenger; C425904:davunetide