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

Takeshi Fujii; Kazuhide Horiguchi; Hiroshi Sunaga; Yasuhiro Moriwaki; Hidemi Misawa; Tadashi Kasahara; Shoutaro Tsuji; Koichiro Kawashima

doi:10.1016/j.jneuroim.2013.12.003

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

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

Authors

Takeshi Fujii¹, Kazuhide Horiguchi², Hiroshi Sunaga³, Yasuhiro Moriwaki⁴, Hidemi Misawa⁴, Tadashi Kasahara⁵, Shoutaro Tsuji⁶, Koichiro Kawashima⁷

Affiliations

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

PMID: 24365495
DOI: 10.1016/j.jneuroim.2013.12.003

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.

Keywords: Acetylcholine; Methyllycaconitine; Mononuclear cells; Proliferation; T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholine / metabolism*
Aconitine / analogs & derivatives
Aconitine / pharmacology
Animals
Antibodies / pharmacology
Antigens, CD / metabolism*
Antigens, Ly / immunology
Antigens, Ly / pharmacology*
Cell Line, Transformed
Cell Proliferation / drug effects
Choline O-Acetyltransferase / genetics
Choline O-Acetyltransferase / metabolism
Dendritic Cells / drug effects*
Dendritic Cells / metabolism
Gene Expression Regulation / drug effects
Humans
Lectins, C-Type / metabolism*
Lymphocytes / drug effects
Lymphocytes / metabolism*
Minor Histocompatibility Antigens
Mitogens / pharmacology
Nicotinic Antagonists / pharmacology
Palatine Tonsil / cytology*
Phytohemagglutinins / pharmacology
RNA, Messenger / metabolism
Radioimmunoassay
Receptors, Cell Surface / metabolism*
Tonsillitis / pathology*
Urokinase-Type Plasminogen Activator / immunology
Urokinase-Type Plasminogen Activator / pharmacology*
alpha7 Nicotinic Acetylcholine Receptor / metabolism

Substances

Antibodies
Antigens, CD
Antigens, Ly
DEC-205 receptor
Lectins, C-Type
Minor Histocompatibility Antigens
Mitogens
Nicotinic Antagonists
Phytohemagglutinins
RNA, Messenger
Receptors, Cell Surface
SLURP1 protein, human
alpha7 Nicotinic Acetylcholine Receptor
methyllycaconitine
Choline O-Acetyltransferase
Urokinase-Type Plasminogen Activator
Acetylcholine
Aconitine