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

MERCURY 217
2. HEALTH EFFECTS
II molecules or modification of self peptides, T-cell receptors, or cell-surface adhesion molecules has been
suggested (Mathieson 1992). The immune suppressive effect of mercury has been examined in human
B-cells (Shenker et al. 1993). This study showed inhibition of B-cell proliferation, expression of surface
antigens, and synthesis of IgG and IgM by both methylmercury and mercuric mercury. These chemicals
caused a sustained elevation of intracellular calcium. Based on concurrent degenerative changes in the
nucleus (hyperchromaticity, nuclear fragmentation, and condensation of nucleoplasm) in the presence of
sustained membrane integrity, the author suggested that the increase in intracellular calcium was initiating
apoptic changes in the B-cells, ultimately resulting in decreased viability.
The glomerulopathy produced by exposure of Brown-Norway rats to mercuric chloride has been related to
the presence of antilaminin antibodies (Icard et al. 1993). Kosuda et al. (1993) suggest that both genetic
background and immune regulatory networks (possibly acting through T-lymphocytes of the RT6 subset)
may play an important role in the expression of autoimmunity after exposure to mercury. A strain (Brown-
Norway) of rats known to be susceptible to mercury-induced production of autoantibodies to certain renal
antigens (e.g., laminin) and autoimmune glomerulonephritis was compared to a nonsusceptible strain
(Lewis). Different responses to subcutaneous injections of mercuric chloride regarding RT6 +
T-lymphocytes (a subpopulation of lymphocytes considered to have possible immunoregulatory properties)
were observed. While a relative decrease in RT6 + T-cells occurring with the development of renal
autoantigen autoimmune responses was observed in the mercury-treated Brown-Norway rats, the Lewis
rats did not develop renal autoimmunity and were found to have undergone significant change in the
RT6 + -to-RT6 + T-lymphocyte ratio. When Brown-Norway-Lewis F1 hybrid rats were similarly dosed,
effects similar to those in the Brown-Norway strain were seen, with the autoimmune responses to kidney
antigens occurring concomitantly with a change in RT6 population proportionally in favor of
T-lymphocytes that do not express the RT6 phenotype. Kosuda et al. (1993) proposed that there are both
endogenous and exogenous components of mercury-induced autoimmunity. The endogenous (a genetically
determined) component includes T-cell receptors, the major histocompatibility complex, and an immunoregulatory
network based upon a rather delicate balance between helper and suppressor (e.g., the RT6 +
T-lymphocytes) cells; whereas the exogenous component is represented by an environmental factor (e.g.,
mercury) capable of altering the balance within the immunoregulatory network. The manifestation of
autoimmunity requires the presence and interaction of both of these components. In a similar study,
Castedo et al. (1993) found that mercuric chloride induced CD4 + autoreactive T-cells proliferate in the
presence of class II + cells in susceptible Brown-Norway rats as well as in resistant Lewis rats. However,
while those cells were believed to collaborate with B-cells in Brown-Norway rats to produce