Expression of acetylcholine in lymphocytes and modulation of an independent lymphocytic cholinergic activity by immunological stimulation
Expression of acetylcholine in lymphocytes and modulation of an independent lymphocytic cholinergic activity by immunological stimulation
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DOI：
10.1163/15693910260698320
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发表时间：
2002-08
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影响因子：
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通讯作者：
T. Fujii;Yoshihiro Watanabe;K. Fujimoto;K. Kawashima
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文献类型：
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作者：
T. Fujii;Yoshihiro Watanabe;K. Fujimoto;K. Kawashima
虽然乙酰胆碱（ACh）被经典地认为是哺乳动物物种中的神经递质，但淋巴细胞具有构成独立的非神经元胆碱能系统所需的大部分组分。这些包括ACh本身、胆碱乙酰转移酶（ChAT）、高亲和力胆碱转运蛋白、乙酰胆碱酯酶以及毒蕈碱和烟碱ACh受体（分别为mAChR和nAChR）。淋巴细胞上的mAChRs和nAChRs的激活可增加细胞内Ca 2+浓度，并刺激c-fos基因表达和一氧化氮合成。虽然在人外周血CD 4+（辅助）T细胞中观察到ChATmRNA的表达，但在CD 8+（细胞毒性）T细胞中未观察到ChATmRNA的表达，但尚不清楚血液ACh的来源是哪些T淋巴细胞亚群。用植物血凝素（一种T细胞激活剂）或结合CD 7和/或CD 11 a细胞表面分子的单克隆抗体刺激淋巴细胞可激活淋巴细胞胆碱能活性，表现为ACh合成和释放增加以及ChAT和M5 mAChR mRNA表达上调。在自发性高血压大鼠和MRL-lpr小鼠这两种免疫紊乱的动物模型中检测到淋巴细胞胆碱能系统的异常。两者合计，这些数据提出了一个令人信服的图片中，免疫功能是，至少部分地，一个独立的非神经元的淋巴细胞胆碱能系统的控制下。
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.