Expression of acetylcholine in lymphocytes and modulation of an independent lymphocytic cholinergic activity by immunological stimulation

Abstract

Although acetylcholine (ACh) is classically thought of as a neurotransmitter in mammalian species, lymphocytes possess most of the components needed to constitute an independent non-neuronal cholinergic system. These include ACh itself, choline acetyltransferase (ChAT), highaffinity choline transporter, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively). Activation of mAChRs and nAChRs on lymphocytes elicits increases in the intracellular Ca2+ concentration and stimulates c-fos gene expression and nitric oxide synthesis. Which subpopulations of T lymphocytes are the source of blood ACh is not yet known, though expression of ChATmRNA was observed in human peripheral CD4+ (helper) but not in CD8+ (cytotoxic) T cells. Stimulation of lymphocytes with phytohemagglutinin, a T-cell activator, or with monoclonal antibodies that bind the CD7 and/or CD11a cell surface molecules activates lymphocytic cholinergic activity, as evidenced by increased synthesis and release of ACh and up-regulation of expression of ChATand M5 mAChR mRNA. Abnormalities in the lymphocytic cholinergic system have been detected in spontaneously hypertensive rats and MRL-lpr mice, two animal models of immune disorders. Taken together, these data present a compelling picture in which immune function is, at least in part, under the control of an independent non-neuronal lymphocytic cholinergic system.