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Expression of Activity-Dependent Neuroprotective Protein in the Immune System: Possible Functions and Relevance to Multiple SclerosisBraitch M.a · Kawabe K.a · Nyirenda M.a · Gilles L.J.a · Robins R.A.b · Gran B.a · Murphy S.c · Showe L.d · Constantinescu C.S.a
aDivision ofClinical Neurology, School of Clinical Sciences, bDivision of Immunology, School of Molecular Medical Sciences, Medical School, Queens Medical Centre, Nottingham University, Nottingham, UK; cDepartment of Neurological Surgery, University of Washington, Seattle, Wash., and dSystemsBiology Division, Genomics Core, The Wistar Institute, Philadelphia, Pa., USA Corresponding Author
Prof. Cris S. Constantinescu
Division of Clinical Neurology, Medical School, B Floor
Queens Medical Centre, Nottingham University, Nottingham NG7 2UH (UK)
Tel. +44 115 875 4597, Fax +44 115 970 9738
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-γ 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-γ in PBMC and caused suppressed anti-CD3-/anti-CD28-stimulated PBMC proliferation. ADNP mRNA was reduced in MS compared to control peripheral blood. Conclusion: 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.
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