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吲哚胺的免疫调节作用:血清素和褪黑素对人外周血单个核细胞DNA及γ-干扰素合成的影响

Immunomodulation by indoleamines: serotonin and melatonin action on DNA and interferon-gamma synthesis by human peripheral blood mononuclear cells.

作者信息

Arzt E S, Fernández-Castelo S, Finocchiaro L M, Criscuolo M E, Díaz A, Finkielman S, Nahmod V E

机构信息

Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), Buenos Aires, República Argentina.

出版信息

J Clin Immunol. 1988 Nov;8(6):513-20. doi: 10.1007/BF00916958.

DOI:10.1007/BF00916958
PMID:3146586
Abstract

Different concentrations of indoleamines, serotonin and melatonin, inhibited phytohemagglutinin stimulated DNA synthesis. Thus, 10(-3) to 10(-4) M of either indoleamine acted at the optimal phytohemagglutinin concentration, while 10(-3) to 10(-7) M acted at suboptimal phytohemagglutinin levels. The serotonin effect was reversed by the serotonergic S1-S2 receptor antagonist methysergide but not by the S2 antagonist ketanserin. This indicates that only the S1 receptor is involved in the inhibitory effect. Inhibition of lymphoproliferation by indoleamines was also exerted on pokeweed mitogen and protein A from Staphylococcus aureus stimulations. Serotonin and melatonin also inhibited phytohemagglutinin and protein A from Staphylococcus aureus induction of interferon-gamma synthesis. The initial uptake of Ca2+ was not affected by indoleamines, suggesting that it is not the mechanism of their inhibitory effects. As interferon-gamma induced tryptophan uptake by T lymphocyte- and macrophage-depleted populations, and tryptophan is the metabolic precursor of serotonin and melatonin, a new immunoregulatory circuit is postulated.

摘要

不同浓度的吲哚胺、血清素和褪黑素可抑制植物血凝素刺激的DNA合成。因此,10⁻³至10⁻⁴M的任何一种吲哚胺在植物血凝素的最佳浓度下起作用,而10⁻³至10⁻⁷M在低于最佳浓度的植物血凝素水平下起作用。血清素的作用可被5-羟色胺能S1 - S2受体拮抗剂美西麦角逆转,但不能被S2拮抗剂酮色林逆转。这表明只有S1受体参与了抑制作用。吲哚胺对淋巴细胞增殖的抑制作用也体现在对商陆有丝分裂原和金黄色葡萄球菌蛋白A刺激的抑制上。血清素和褪黑素也抑制植物血凝素和金黄色葡萄球菌蛋白A诱导的γ-干扰素合成。Ca²⁺的初始摄取不受吲哚胺的影响,这表明这不是它们产生抑制作用的机制。由于γ-干扰素可诱导色氨酸在耗尽T淋巴细胞和巨噬细胞的群体中的摄取,且色氨酸是血清素和褪黑素的代谢前体,因此推测存在一种新的免疫调节回路。

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