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J Neuroimmunol. 2014 Feb 15;267(1-2):43-9. doi: 10.1016/j.jneuroim.2013.12.003. Epub 2013 Dec 11.

SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205(+) dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity.

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  • 1Department of Pharmacology, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
  • 2Division of Anatomy and Neuroscience, Department of Morphological and Physiological Sciences, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui 910-1193, Japan.
  • 3Department of Otorhinolaryngology, Head and Neck Surgery, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui 910-1193, Japan.
  • 4Department of Pharmacology, Keio University Faculty of Pharmacy, Minato-ku, Tokyo 105-8512, Japan.
  • 5Department of Biochemistry, Keio University Faculty of Pharmacy, Minato-ku, Tokyo 105-8512, Japan.
  • 6Molecular Diagnostics Project, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa 241-0815, Japan.
  • 7Department of Molecular Pharmacology, Kitasato University of Pharmaceutical Sciences, Minato-ku, Tokyo 108-8641, Japan. Electronic address: koichiro-jk@piano.ocn.ne.jp.

Abstract

Immune cells often express various nicotinic ACh receptor (nAChR) subtypes, including α7 nAChRs, as well as mRNA encoding secreted lymphocyte antigen-6/urokinase-type plasminogen activator receptor-related peptide (SLURP)-1, an endogenous α7 nAChR allosteric ligand. We detected SLURP-1 immunoreactivity in CD205(+) dendritic cells (DCs) residing in human tonsils. Phytohemagglutinin (PHA, 10 μg/ml), a T cell activator, attenuated cell proliferation and increased the ACh content of MOLT-3 human leukemic T cells compared with the vehicle control. Methyllycaconitine (MLA, 100nM), a specific α7 nAChR antagonist, abolished all effects elicited by PHA. Recombinant (r)SLURP-1 (0.5 μg/ml) attenuated peripheral blood mononuclear cell proliferation and increased ChAT gene expression and the ACh content in MOLT-3 cells compared with the control, all of which were abolished by MLA. This suggests SLURP-1 activates cholinergic transmission by potentiating ACh synthesis and its action at α7 nAChRs, thereby facilitating functional development of T cells. These findings support the notion that SLURP-1 acts as a key modulator of immune responses.

Copyright © 2013 Elsevier B.V. All rights reserved.

KEYWORDS:

Acetylcholine; Methyllycaconitine; Mononuclear cells; Proliferation; T cells

PMID:
24365495
[PubMed - indexed for MEDLINE]
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