淋巴细胞合成的内源性儿茶酚胺对T细胞增殖功能的影响

目的：提供淋巴细胞合成儿茶酚胺（CAs）的证据,并探讨淋巴细胞合成的内源性CAs对淋巴细胞自身功能的影响及其受体介导机制。方法：用RT-PCR技术检测CAs合成的限速酶酪氨酸羟化酶（TH）mRNA在大鼠肠系膜淋巴结细胞内的表达。用单胺氧化酶（CAs降解酶）的抑制剂优降宁及α1、α2、β1和β2肾上腺素受体（AR）的拮抗剂作用于淋巴细胞．然后用四唑蓝比色法测定淋巴细胞对刀豆蛋白A（ConA）刺激的增殖反应。结果：大鼠肠系膜淋巴结细胞具有,TH mRNA的表达,并且淋巴细胞在用ConA刺激活化后,其TH mRNA的表达明显上调。10^-6和10^-5mol／L优降宁能显著抑制ConA诱导的T淋巴细胞增殖,而10^-7mol／L优降宁不能明显降低T淋巴细胞的增殖反应。β2-AR拮抗剂ICI 118551（10^-7和10^-6mol／L）可完全阻断优降宁（10^-5mol／L）对T细胞增殖的抑制作用;α1-AR拮抗剂柯喃因和α2-AR拮抗剂育亨宾部分阻断优降宁抑制T细胞增殖的作用;而β1-AR拮抗剂阿替洛尔不能阻断优降宁的抑制作用。结论：淋巴细胞具有合成CAs的能力,这种合成能力随着淋巴细胞的激活而明显增强。淋巴细胞合成的内源性CAs可能通过自分泌或／和旁分泌路径主要激活淋巴细胞上的β2-AR,从而抑制T细胞的增殖反应。

Effect of the endogenous catecholamines synthesized by lymphocytes on T cell proliferation

Aim： To provide further evidence for the synthesis of catecholamines（CAs） in lymphocytes and to investigate the effect of the endogenous CAs synthesized by lymphocytes on function of the lymphocytes themselves and the receptor mechanisms involved in the effect. Methods： RT- PCR was performed to detect the expression of TH mRNA in the lymphocytes from the mesenteric lymph nodes of rats. Different concentrations of pargyline, an inhibitor of monoamine oxydase, and antagonists of α1-, α2-, β1-, and β2-adrenergic receptor（AR） were added to the lympho- cyte cultures, and then proliferative response of the lymphocytes to mitogen concanavalin A（Con A） were measured via methyl-thiazole-tetra- zohum（MTT） assay. Results： The lymphocytes could express TH mRNA, and the expression of TH mRNA was significantly higher in the Con A-activated lymphocytes than in the resting ones. The treatment of pargyline of 10^-6 and 10^-5 mol/L（ not 10^-7 mol/L） notably attenuated Con Ainduced lymphocyte proliferation.β2-AR antagonist ICI118551（ 10^-7 and 10^-6 mol/L） completely blocked, but α1-AR antagonist corynanthine and α2-AR antagonist yohimbine（ 10^-7 and 10^-6 mol/L） partly blocked the suppressive effect of pargyhne on the Con A-induced lymphocyte pro- liferation. Nevertheless, atenolol, an antagonist of β1-AR, had no blocking effect on pargyline inhibition of lymphocyte proliferation. Conclusion： Lymphocytes have the ability to synthesize CAs and the ability is enhanced in the activated lymphocytes. The endogenous CAs synthe- sized by lymphocytes can inhibit T cell proliferation and the inhibition of T cells by the CAs is mediated predominantly by β2-AR on the lymphoeytes.