revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 218
2. HEALTH EFFECTS
autoantibodies, in Lewis rats they apparently initiate a suppressor circuit involving antiergotypic CD8 +
suppressor cells.
In Brown-Norway rats given 5 subcutaneous 1 mg/kg injections of mercuric chloride over a 10-day period,
tissue injury (including vasculitis) was seen within 24 hours of the first injection (Qasim et al. 1995). The
rapid onset of tissue injury suggests that cells other than T-cells may be involved in the primary induction
of vasculitis typically seen as a response to mercuric chloride in this species. It is possible that this injury
occurs through a direct action of HgCl 2 on neutrophils or through activation of mast cells, resulting in the
release of TNF and IL8, which promote chemotaxis and activation of neutrophils. However, the changes in
the Th2-like (CD4+CD45) T-cell subsets seen in this study were considered to provide support for the
hypothesis that a rise in T helper cells drives the observed autoimmune syndrome, providing B-cell help,
which leads to polyclonal activation and production of a range of antibodies.
Jiang and Moller (1995) found that mercuric chloride induced increased DNA synthesis in vitro (peak
activity between days 4 and 6) in lymphocytes from several mouse strains and suggested a crucial role for
helper T-cells in HgCl2-induced immunotoxicity. The results of this study indicated that: (1) mercuric
chloride activated CD4+ and CD8+ T-cells (in vitro) in a manner analogous to a specific antigen-driven
response; (2) activation was dependent upon the presence of accessory cells; and (3) helper T-cells were
induced to divide and transform in responder organ cells. This led Jiang and Moller (1995) to hypothesize
that mercury binds to molecules on the antigen-presenting cell (APC) and transforms molecules on these
cells to superantigens capable of activating T-cells with a particular set of antigen-binding receptors. In this
manner, mercury could induce an internal activation of the immune system, which would in turn result in a
variety of symptoms in predisposed individuals.
Both mercuric chloride (1 µM) and methylmercury (2 µM) have been shown to increase intracellular Ca ++
concentrations in splenic lymphocytes in a concentration-dependent manner (Tang et al. 1993). The time
course for the effect was, however, different for the two mercurials. In the case of methylmercury, the
increase in intracellular Ca ++ was rapid and the increased level was sustained over time, whereas the Ca ++
rise caused by HgCl2 was slower. While the effects of those mercurials did not appear to be associated
with alterations of membrane integrity, both HgCl2 and methylmercury did appear to cause membrane
damage when the incubation time was extended. This study also found that methylmercury and mercuric
chloride appear to exert their effects on internal lymphocyte Ca ++ levels in different ways. Methylmercury
increases intracellular Ca ++ by both an apparent increase in the permeability of the membrane to