IMMUNOMODULATORY ACTIVITIES OF EXTRACELLULAR METALLOTHIONEIN .1. METALLOTHIONEIN EFFECTS ON ANTIBODY-PRODUCTION
IMMUNOMODULATORY ACTIVITIES OF EXTRACELLULAR METALLOTHIONEIN .1. METALLOTHIONEIN EFFECTS ON ANTIBODY-PRODUCTION
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DOI：
10.1016/0300-483x(93)90040-y
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发表时间：
1993-12-31
期刊：
影响因子：
4.5
通讯作者：
OLSON, EA
中科院分区：
文献类型：
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作者：
LYNES, MA;BORGHESI, LA;OLSON, EA
细胞外金属硫蛋白（Zn，Cd-MT）先前已被证明是淋巴细胞增殖的有效诱导剂，并在增殖测定中与多克隆活化剂协同作用。在这份报告中，金属硫蛋白对体液反应性的发展的影响进行了检查。在体内，特异性抗卵清蛋白（OVA）IgG反应减少共注射锌，镉-MT，而总：IgG水平保持不变。当在抗绵羊红细胞（sRBC）体液应答的发展过程中给予Zn，Cd-MT时，也观察到类似的减少。当与Zn、Cd-MT等摩尔量的Zn、Cd与OVA共同注射时，体液反应性增强，而Zn、Cd-MT抑制则相反。Apothionein缺乏与天然Zn，Cd-MT相关的有效巯基，对体液免疫的发展没有影响。这些结果表明，与蛋白质相关的巯基是观察到的免疫抑制中的重要决定因素，这得到了UC 1 MT（一种新的单克隆抗MT抗体）逆转MT介导的免疫抑制的能力的支持。没有证据表明Zn、Cd-MT与OVA直接相互作用。最后，在体外实验中，LPS刺激的脾细胞产生的IgM与体内观察的Zn，Cd-MT。这些数据提供了证据MT在金属介导的免疫调节的发展中的重要作用，并表明MT也可能具有免疫调节功能的情况下，MT是在没有重金属胁迫下合成的。此外，有可能利用该系统来外源性地操纵免疫应答的发展。
Extracellular metallothionein (Zn,Cd-MT) has previously been shown to be a potent inducer of lymphocyte proliferation and to synergize with polyclonal activators in proliferation assays. In this report, the effects of metallothionein on the development of humoral responsiveness are examined. In vivo, the specific anti-ovalbumin (OVA) IgG response was diminished by co-injection of Zn, Cd-MT, while total:IgG levels remained unchanged. A similar reduction was also observed when Zn,Cd-MT; was administered during the development of an anti-sheep red:blood cell (sRBC)humoral response. When amounts of Zn and Cd equimolar to that associated with the Zn, Cd-MT were co-injected with OVA, humoral responsiveness was enhanced, in contrast to the suppression seed with Zn, Cd-MT. Apothionein lacking the available thiols associated with native Zn, Cd-MT had no effect on the development of humoral immunity. These results point to the thiols associated with the protein as the important determinants in the observed immunosuppression and this is supported by the capacity of UC1MT, a new monoclonal anti-MT antibody; to reverse MT mediated immunosuppression. No evidence was found to suggest that Zn,Cd-MT was interacting directly with OVA. Finally, in vitro experiments with, LPS-stimulated splenocyte production of IgM correlated with the in vivo observations of Zn,Cd-MT. These data provide evidence for a significant role for MT in the development of metal-mediated immunomodulation and suggest that MT may also possess immunomodulatory functions under circumstances where MT is synthesized in the absence of heavy metal stress. Furthermore, it may be possible to take advantage of this system to exogenously manipulate the development of the immune response.