title: SLURP-1, an endogenous α7 nicotinic acetylcholine receptor allosteric ligand, is expressed in CD205(+) dendritic cells in human tonsils and potentiates lymphocytic cholinergic activity.
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.
authors.affiliation: Department of Pharmacology, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Division of Anatomy and Neuroscience, Department of Morphological and Physiological Sciences, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Horiguchi
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University of Fukui Faculty of Medical Sciences, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sunaga
authors.affiliation: Department of Pharmacology, Keio University Faculty of Pharmacy, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Moriwaki
authors.affiliation: Department of Pharmacology, Keio University Faculty of Pharmacy, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.affiliation: Department of Biochemistry, Keio University Faculty of Pharmacy, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.affiliation: Molecular Diagnostics Project, Kanagawa Cancer Center Research Institute, Yokohama, Kanagawa 241-0815, Japan.
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Department of Molecular Pharmacology, Kitasato University of Pharmaceutical Sciences, Minato-ku, Tokyo 108-8641, Japan. Electronic address: koichiro-jk@piano.ocn.ne.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawashima
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D000950:Antigens, Ly / Q000276:immunology / Q000494:pharmacology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D008934:Mitogens / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D014066:Palatine Tonsil / Q000166:cytology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014069:Tonsillitis / Q000473:pathology*; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000494:pharmacology*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000950:Antigens, Ly; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D008934:Mitogens; D018733:Nicotinic Antagonists; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C048963:SLURP1 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D002795:Choline O-Acetyltransferase; D014568:Urokinase-Type Plasminogen Activator; D000109:Acetylcholine; D000157:Aconitine
keywords: Acetylcholine; Methyllycaconitine; Mononuclear cells; Proliferation; T cells