[An independent, non-neuronal cholinergic system in lymphocytes and its roles in regulation of immune function].
Acetylcholine (ACh) is classically thought of as a neurotransmitter in mammalian species. However, lymphocytes express most of the cholinergic components found in the nervous system, including ACh, choline acetyltransferase (ChAT), high-affinity choline transporter, and acetylcholinesterase as well as both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Activation of T cells via the T cell receptor/CD3 complex, contact of T cells with antigen presenting cells, or activation of the adenylyl cyclase pathway in T cells modulates cholinergic activity, as evidenced by up-regulation of ChAT and M(5) mAChR mRNA expression. Stimulation of mAChRs on T and B cells with ACh or another mAChR agonists elicits intracellular Ca(2+) signaling, up-regulation of c-fos expression, increased nitric oxide synthesis and interleukin-2-induced signal transduction via M(3) and M(5) mAChR-mediated pathways. Acute stimulation of nAChRs with ACh or nicotine causes rapid and transient Ca(2+) signaling in T and B cells, probably via alpha7 nAChRs subunit-mediated pathways. Chronic nicotine stimulation, by contrast, down-regulates nAChR expression and suppresses T cell activity. Abnormalities in lymphocytic cholinergic system have been seen in animal models of immune deficiency and immune acceleration. Collectively, these data provided a compelling picture in which immune function is, at least partly, under the control of an independent, non-neuronal cholinergic system in lymphocytes.
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan. fujii-tk@kyoritsu-ph.ac.jp
Takeshi
T
Fujii
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000502:physiology
D011950:Receptors, Cholinergic; D000109:Acetylcholine