Daum J R, Shepherd D M, Noelle R J
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756.
Int J Immunopharmacol. 1993 Apr;15(3):383-94. doi: 10.1016/0192-0561(93)90049-5.
Heavy metals have been shown to exert immunotoxic effects on humoral immunity. To ascertain the mechanisms by which these immunotoxic effects are exerted, the effects of CdCl2 and HgCl2 on the biology of murine B-lymphocytes were studied. It was shown that CdCl2 and HgCl2 inhibited B-cell RNA and DNA synthesis. The IC50 (the concentration required to inhibit a specific B-cell function by 50%) for CdCl2 was 30 microM for RNA synthesis and DNA synthesis. The IC50 for HgCl2 was 50 and 120 nM for RNA and DNA synthesis, respectively. Cell cycle analysis revealed that B-cells were arrested throughout the cell cycle with CdCl2 and HgCl2. The inhibitory effects exerted by CdCl2 and HgCl2 were rapid, inhibiting RNA synthesis within 2 h of activation. Differentiation to Ig secretion was inhibited by CdCl2 and HgCl2 in culture and there appeared to be selective effects on specific Ig isotypes. IgG3 production was most sensitive to inhibition by CdCl2 and HgCl2 followed by IgG1 and IgG2b and then IgM and IgG2a. Changes in the expression of B-cell surface antigens induced by LPS were also influenced by CdCl2. LPS-induced increases in class II MHC expression was inhibited by CdCl2, as was the constitutive expression of class I MHC antigen. A summary of the IC50 for CdCl2 and HgCl2 are presented. In summary, both CdCl2 and HgCl2 exert early, inhibitory effects on B-cell activation. This is manifested by the inhibition of RNA, DNA and antibody synthesis. However, selective effects on the production of specific Ig isotypes by these metals may influence the ability of B-cells to mount effective immune responses to pathogens.
重金属已被证明对体液免疫具有免疫毒性作用。为了确定这些免疫毒性作用的发挥机制，研究了氯化镉（CdCl₂）和氯化汞（HgCl₂）对小鼠B淋巴细胞生物学特性的影响。结果表明，CdCl₂和HgCl₂抑制B细胞的RNA和DNA合成。CdCl₂对RNA合成和DNA合成的半数抑制浓度（IC₅₀，即抑制特定B细胞功能50%所需的浓度）为30 μM。HgCl₂对RNA和DNA合成的IC₅₀分别为50 nM和120 nM。细胞周期分析显示，CdCl₂和HgCl₂使B细胞在整个细胞周期中停滞。CdCl₂和HgCl₂的抑制作用迅速，在激活后2小时内即可抑制RNA合成。在培养过程中，CdCl₂和HgCl₂抑制向Ig分泌的分化，并且似乎对特定的Ig同种型有选择性作用。IgG₃的产生对CdCl₂和HgCl₂的抑制最为敏感，其次是IgG₁和IgG₂b，然后是IgM和IgG₂a。CdCl₂还影响脂多糖（LPS）诱导的B细胞表面抗原表达的变化。CdCl₂抑制LPS诱导的II类主要组织相容性复合体（MHC）表达增加，以及I类MHC抗原的组成性表达。文中列出了CdCl₂和HgCl₂的IC₅₀总结。总之，CdCl₂和HgCl₂均对B细胞激活产生早期抑制作用。这表现为对RNA、DNA和抗体合成的抑制。然而，这些金属对特定Ig同种型产生的选择性作用可能会影响B细胞对病原体产生有效免疫反应的能力。
