Shenker B J, Berthold P, Rooney C, Vitale L, DeBolt K, Shapiro I M
Department of Pathology, University of Pennsylvania School of Dental Medicine, Philadelphia 19104-6002.
Immunopharmacol Immunotoxicol. 1993 Jan;15(1):87-112. doi: 10.3109/08923979309066936.
The major goal of the study was to determine the effects of high and low levels of mercury on human B-cells. Following treatment of B-cells with HgCl2 (0-1000 ng) and MeHgCl2 (0-100 ng), their activation by mitogens was evaluated. Both forms of mercury caused a dose dependent reduction in B-cell proliferation in the presence or absence of monocytes. MeHgCl was approximately 10 times more potent than HgCl2. Mercury also inhibited the ability of these cells to synthesize IgM and IgG. Analysis of the expression of activation markers indicated that CD69, an early marker of cell activation, was not effected by mercury. In comparison, B-cell expression of the low affinity IgE receptor and the transferrin receptor were significantly reduced. Of particular interest, cells activated by mitogen for 48 hr became refractory to the immunotoxic effects of mercury. When exposed to high levels of HgCl2 (0.5-10 micrograms/ml) and MeHgCl (0.05-1 micrograms/ml), there was minimal reduction in B-cell viability at 1-4 hr, however, after exposure to mercury for 24 hr, cell death was apparent. MeHgCl was approximately 5-10 times more potent than HgCl2. Electron microscopic analysis revealed early nuclear alterations characterized by hyperchromaticity, nuclear fragmentation and condensation of nucleoplasm. Both forms of mercury caused a rapid and sustained elevation in the intracellular levels of Ca++. The results of this investigation clearly show that mercury-containing compounds are immunomodulatory; moreover, the decrease in B-cell function indicates that this metal is immunotoxic at very low exposure levels. Furthermore, the cytotoxic events are consistent with the notion that mercury initiates changes associated with programmed cell death.
该研究的主要目标是确定高剂量和低剂量汞对人类B细胞的影响。在用HgCl2（0 - 1000纳克）和甲基汞（0 - 100纳克）处理B细胞后，评估它们被丝裂原激活的情况。在有或没有单核细胞存在的情况下，两种形式的汞均导致B细胞增殖呈剂量依赖性降低。甲基汞的效力约为HgCl2的10倍。汞还抑制这些细胞合成IgM和IgG的能力。对激活标志物表达的分析表明，细胞激活的早期标志物CD69不受汞的影响。相比之下，低亲和力IgE受体和转铁蛋白受体的B细胞表达显著降低。特别有趣的是，被丝裂原激活48小时的细胞对汞的免疫毒性作用变得不敏感。当暴露于高剂量的HgCl2（0.5 - 10微克/毫升）和甲基汞（0.05 - 1微克/毫升）时，在1 - 4小时内B细胞活力的降低最小，然而，在暴露于汞24小时后，细胞死亡明显。甲基汞的效力约为HgCl2的5 - 10倍。电子显微镜分析显示早期核改变，其特征为核染色质增多、核碎裂和核质凝聚。两种形式的汞均导致细胞内Ca++水平迅速且持续升高。这项研究的结果清楚地表明含汞化合物具有免疫调节作用；此外，B细胞功能的降低表明这种金属在极低暴露水平下具有免疫毒性。此外，细胞毒性事件与汞引发与程序性细胞死亡相关变化的观点一致。
