Immunotoxic Effects of Mercuric Compounds on Human Lymphocytes and Monocytes. IV. Alterations in Cellular Glutathione Content

Abstract

The major goal of this investigation was to determine if the sensitivity of lymphocytes and monocytes to mercury (Hg⁺⁺) was related to intracellular glutathione² (GSH) levels and the thiol redox status [GSH/glutathione disulfide (GSSG)]. To isolate cells based upon their GSH content, T and B-cells were stained with monochlorobimane (MCB) and separated into high and low fluorescent groups by FACS analysis. Cells with high GSH fluorescence were found to be resistant to both the cytotoxic and immunotoxic effects of HgCl₂ as evidenced by cell viability and their responsiveness to mitogen, respectively. In contrast, cells with low levels of GSH were extremely sensitive to mercury. To further examine the relationship between GSH level and mercury exposure, T-cells, B-cells and monocytes were treated with different doses of HgCl₂ for 12 hrs. All cells exhibited a dose-dependent decrease in GSH content with a concomitant reduction in GSSG levels. However, the GSH/GSSG ratio in these cells remained constant, or increased following exposure to mercury. GSH levels were also reduced in monocytes following exposure to HgCl₂; in this case, GSSG levels remained constant and a decline in the GSH/GSSG ratio was observed. For all cell types, mercury did not inhibit the activities of GSH reductase and GSH peroxidase, enzymes responsible for oxidation/reduction of GSH and GSSG, respectively. Results of the study clearly show that susceptibility to the immunotoxic effects of HgCl₂ is, in part, dependent upon GSH levels and further that mercury inhibits GSH generation by lymphocytes and monocytes. Whether a decrease in GSH or a change in the thiol redox state causes functional deficits associated with low level mercury exposure remains to be determined.