IMR Press / FBL / Volume 9 / Issue 3 / DOI: 10.2741/1390

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Expression of non-neuronal acetylcholine in lymphocytes and its contribution to the regulation of immune function
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1 Department of Pharmacology, Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan
Academic Editor:Sergei Grando
Front. Biosci. (Landmark Ed) 2004, 9(3), 2063–2085;
Published: 1 September 2004
(This article belongs to the Special Issue Nonneuronal acetylcholine in normal physiology and pathology)

Lymphocytes express most components of the cholinergic system including acetylcholine (ACh), muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively), choline acetyltransferase (ChAT), high affinity choline transporter and acetylcholinesterase. ACh and mAChR agonists elicit intracellular Ca2+ signaling, up-regulation of c-fos expression and nitric oxide synthesis within T and B cells probably via M3 and M5 mAChRs. Stimulation of nAChRs with ACh or nicotine causes a rapid and transient Ca2+ signaling in T and B cells, probably via alpha7 nAChR subunit-mediated pathways. Phytohemagglutinin- or antigen-induced T cell activation via cell surface molecules (e.g., T cell receptor/CD3 complexes) enhances lymphocytic cholinergic transmission by up-regulating ChAT and M5 mAChR expression. It is thus likely that a local lymphocytic cholinergic system is involved in regulating immune function. This idea is supported by the findings that lymphocytic cholinergic activity is altered in animal models exhibiting immunological abnormalities. In addition, it appears likely that during interactions mediated by cell surface molecules T cells communicate via ACh with thymic epithelial cells and vascular endothelial cells, which also express ChAT and nAChRs or mAChRs. This interaction leads to T cell selection and maturation in the thymus and local vascular smooth muscle relaxation. Collectively, these data provide a compelling picture in which lymphocytes constitute a cholinergic system that is independent of cholinergic nerves, and which is involved in the regulation of immune function and local circulation.

Antigen presentation
B cell
Choline Acetyltransferase
High affinity choline transporter
Muscarinic receptor
Nicotinic receptor
Nitric oxide
Spontaneously hypertensive rat
T cell
Thymic epithelial cell
Vascular endothelial cell
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