title: Acetylcholine released from T cells regulates intracellular Ca2+, IL-2 secretion and T cell proliferation through nicotinic acetylcholine receptor.
abstract: OBJECTIVE
  T lymphocytes synthesize acetylcholine (ACh) and express muscarinic and nicotinic ACh receptors (mAChR and nAChR, respectively) responsible for increases in the intracellular Ca2+concentration ([Ca2+]i). Our aim in the present study was to assess whether autocrine ACh released from T lymphocytes regulates their physiological functions.
  
  
  METHODS
  MOLT-3 human leukemic cell line and murine splenocytes were loaded with fura-2 to monitor [Ca2+]ichanges in the absence or presence of several AChR antagonists, including mecamylamine, methyllycaconitine and scopolamine. Real-time PCR and ELISA were performed to measure interleukin-2 (IL-2) mRNA and protein levels.
  
  
  RESULTS
  T lymphocytes constitutively produce sufficient amounts of ACh to elicit autocrine changes in [Ca2+]i. These autocrine ACh-evoked [Ca2+]itransients were mediated by nAChRs and then influx of extracellular Ca2+. Mecamylamine, a nAChR inhibitor, suppressed not only these [Ca2+]itransients, but also IL-2 release and T cell proliferation.
  
  
  CONCLUSIONS
  Here, we confirmed that T lymphocytes utilize ACh as a tool to interact with each other and that autocrine ACh-activated nAChRs are involved in cytokine release and cell proliferation. These findings suggest the possibility that nAChR agonists and antagonists and smoking are able to modulate immune function, which in turn suggests the therapeutic potential of immune activation or suppression using nAChR agonists or antagonists.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, 610-0395, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Mashimo
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, 610-0395, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, 610-0395, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, 610-0395, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Molecular Pharmacology, Kitasato University School of Pharmaceutical Sciences, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kawashima
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto, 610-0395, Japan. Electronic address: tfujii@dwc.doshisha.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018722:Nicotinic Agonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D002118:Calcium
keywords: Acetylcholine; Interleukin-2; Nicotinic acetylcholine receptor; Spontaneous [Ca(2+)](i) increase; T cells