Cholinergic System in Lymphocytes

MARIA DEL CARMEN, ESANDI; MARIA JOSE, DE ROSA; CECILIA, BOUZAT

"New Research on Neuroimmunology"

Nova Science Publishers

Lugar: New York; Año: 2006;

Acetylcholine (ACh) plays an important role as a neurotransmitter of the central and peripheral nervous systems. Interestingly, this molecule and its synthesizing enzyme, choline acetyltransferase, are also present in lymphocytes. In addition, several types of nicotinic (nAChR) and muscarinic (mAChR) receptors have been identified in these blood cells. These findings have provided evidence that lymphocytes have most of the essential components needed to constitute a non neuronal cholinergic system. However, the precise role of this extraneuronal cholinergic system is poorly understood. ACh may act as an immunomodulator. Activated immune cells may use the released ACh in self-modulating autocrine and paracrine loops. Upon phytohemagglutinin (PHA) stimulation of human lymphocytes an increment in the synthesis of ACh occurs, suggesting that the neurotransmitter modulates T-cell activation. Different subtypes of mAChRs are present in lymphocytes. mAChRs are involved in lymphocyte activation by enhancing T cell antigen receptor/CD3-induced IL-2 production. Different nAChR subtypes have been reported in blood cells although their patterns of expression and function remain unknown. a7 nAChR mRNA has been detected in peripheral human lymphocytes. Nicotine, probably acting through a7 nAChRs, elicits transient increases in Ca2+ in mononuclear leukocytes and human leukemic cell lines. Nicotine and the antagonist á-bungarotoxin lead to up-regulation of a7 and to a concomitant protection of lymphocytes from cortisol-induced apoptosis, suggesting that a7 is involved in the modulation of this process. In summary, in addition to the recognized cytokine network, the extraneuronal cholinergic system plays a key role in the regulation of the immune function. The extraneuronal cholinergic system could function independently or coordinated with the neural system. It is interesting to note that lymphocytes may reflect the metabolism of brain cells and this may be exploited as a neural and possible genetic probe in studies of psychiatric disorders.