Borghesi L A, Lynes M A
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269, USA.
Toxicol Appl Pharmacol. 1996 Jul;139(1):6-14. doi: 10.1006/taap.1996.0137.
Metallothionein (MT) is a small, cysteine-rich protein that is readily induced by exposure to heavy metal cations. In previous work, we have demonstrated that MT has several significant immunomodulatory properties. MT decreases antigen-specific humoral responses in vivo and inhibits the ability of T cells to proliferate in response to antigen presented in vitro. To further characterize the mechanism by which this protein inhibits responsiveness to antigen, we have examined the effects of MT on cell viability in an antigen-presentation assay. MT (20 microM) caused substantial death to both lymphocytes and monocytes after 3 days of culture. The observed toxicity cannot be attributed to either increased superoxide radical generation or to production of tumor necrosis factor by MT-treated macrophages. Fractionation of supernatants from MT-treated cells suggests that the agent responsible for causing cytotoxicity is a soluble factor of at least 30 kDa. These results counter the perception that metallothionein uniformly plays a protective role in metal-stressed individuals.
金属硫蛋白（MT）是一种富含半胱氨酸的小蛋白，暴露于重金属阳离子时很容易被诱导产生。在之前的研究中，我们已经证明MT具有多种重要的免疫调节特性。MT可降低体内抗原特异性体液反应，并抑制T细胞在体外对抗原呈递做出反应时的增殖能力。为了进一步阐明这种蛋白抑制对抗原反应性的机制，我们在抗原呈递试验中研究了MT对细胞活力的影响。培养3天后，20微摩尔的MT导致淋巴细胞和单核细胞大量死亡。观察到的毒性既不能归因于超氧自由基生成增加，也不能归因于MT处理的巨噬细胞产生肿瘤坏死因子。对MT处理细胞的上清液进行分级分离表明，导致细胞毒性的因子是一种至少30千道尔顿的可溶性因子。这些结果与金属硫蛋白在金属应激个体中始终发挥保护作用的观点相悖。
