Department of Pharmacology, Medical School, University of Athens, M. Asias 75, 11527 Athens, Greece.
J Trace Elem Med Biol. 2011 Jul;25(3):138-42. doi: 10.1016/j.jtemb.2011.07.002. Epub 2011 Aug 30.
The trace element molybdenum (Mo) is an essential component of key physiological systems in animals, plants and microorganisms. The molybdate oxoanion MoO(4)(2-) has been demonstrated to cause diverse yet poorly understood biochemical and pharmacological effects, such as non-specific inhibition of phosphatases and stabilization of steroid receptors. This study aimed to investigate the effects of molybdate on the activation of human peripheral blood lymphocytes (hPBLs) ex vivo and its potential interaction with the widely used immunosuppressant drug cyclosporin A (CsA). Lymphocyte activation was evaluated by performing multiple experiments determining blastogenesis in cultured peripheral blood lymphocytes obtained from 5 healthy volunteers, following stimulation induced by phytohemagglutinin (PHA), in the absence or presence of 0.05-10 mM sodium molybdate or/and 2.5-30 μg/mL CsA. Blastogenesis was assessed by a morphometric assay based on the relative proportions of unactivated lymphocytes, activated lymphoblasts and cells with aberrant morphology after PHA-induced activation. Molybdate concentrations up to 1 mM showed no effect on lymphocyte blastogenesis, while higher concentrations exerted immunosuppressive actions on cultured hPBLs. Co-administration of 0.1 mM sodium molybdate with CsA, at doses up to 20 μg/mL, induced no alteration in the response of cultured hPBLs to CsA. However, molybdate potentiated the immunosuppressive action of higher CsA concentrations, implying a likely dose-related synergistic interaction of the two agents in PHA-stimulated blood lymphocytes. These observations are indicative of the possible biological importance of molybdate oxoanions in the modulation of hPBL activation that may have pharmacological consequences during the therapeutic application of immunomodulatory drugs.
微量元素钼（Mo）是动物、植物和微生物中关键生理系统的必需组成部分。钼酸盐氧阴离子 MoO(4)(2-) 已被证明会引起多种但尚未完全了解的生化和药理作用，例如对磷酸酶的非特异性抑制和类固醇受体的稳定。本研究旨在研究钼酸盐对人外周血淋巴细胞（hPBL）体外激活的影响及其与广泛使用的免疫抑制剂药物环孢素 A（CsA）的潜在相互作用。通过对 5 名健康志愿者的外周血淋巴细胞进行培养，在植物血凝素（PHA）诱导下，在不存在或存在 0.05-10 mM 钼酸钠或/和 2.5-30 μg/mL CsA 的情况下进行多项实验来评估淋巴细胞的激活，以确定细胞的有丝分裂。通过基于 PHA 诱导激活后未激活淋巴细胞、活化淋巴母细胞和形态异常细胞的相对比例的形态计量测定法评估有丝分裂。浓度高达 1 mM 的钼酸盐对淋巴细胞有丝分裂没有影响，而较高浓度对培养的 hPBL 具有免疫抑制作用。在高达 20 μg/mL 的 CsA 剂量下，与 0.1 mM 钼酸钠共同给药不会改变培养的 hPBL 对 CsA 的反应。然而，钼酸盐增强了较高 CsA 浓度的免疫抑制作用，这意味着两种药物在 PHA 刺激的血液淋巴细胞中可能存在剂量相关的协同相互作用。这些观察结果表明钼酸盐氧阴离子在调节 hPBL 激活方面可能具有生物学重要性，这可能在免疫调节药物的治疗应用中具有药理后果。
