Autoimmunity mercury-induced

Balazs, T.Jmmunogenetically controlled autoimmune reactions induced by mercury, gold and D-penicillamine in laboratory animals A review from the vantage point of premarketing safety studies. Toxicol. Ind. Health., 3, 331, 1987... 

Kosuda, L.L.et al., (1994) Role of RT6+ T lymphocytes in mercury-induced renal autoimmunity Experimental manipulations of susceptible and resistant rats. J. Toxicol. Environ. Health, 42, 303, 1994. 

Hultman, P., and Enestrom, S., Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease. Toxicol. Appl. Pharmacol., 113, 199, 1992... 

Zargari, A., Gharibdoost, F., DePierre, J.W. and Flassan, M. (2005) Bacterial lipopolysaccharide both renders resistant mice susceptible to mercury-induced autoimmunity and exacerbates such autoimmunity in susceptible mice. Clinical and Experimental Immunology, 141, 238-247. 

Haggqvist B, Hultman P Effects ofdeviatingtheTh2-response In murine mercury-induced autoimmunity towards aThI-response. Clin Exp Immunol 2003 134 202-9. 

Zheng Y, Jost M, Gaughan JP, Class R, Coyle AJ, Monestler M ICOS-B7 homologous protein Interactions are necessary for mercury-induced autoimmunity. J Immunol 2005 174 3117-21. 

Zheng Y, Monestler M Inhibitory signal override Increases susceptibility to mercury-induced autoimmunity. J Immunol 2003 171 1596-601. 

Pillion J, Baccala R, Kuhn J, Druet P, Bellon B Evidence for heterogenous TCRVb expression in mercury-induced autoimmune disorders in rats. Int. Immunol. 1997 9 263-271. 

Pelletier L, Pasquier R, Rossert J,Vial M-C, Mandet C, Druet P AutoreactiveT cells in mercury-induced autoimmunity. Ability to induce the autoimmune disease. J. Immunol. 1988 140 750-4. 

Over the past decade there has, as result of experimental studies, been a growing appreciation that mercury may exert an effect on the immune system. As summarized by Silbergeld and Devine [72], mercury has at least two types of effects on the immune system. First, mercury induces autoimmunity to renal basement membrane proteins, causing mercury-induced glomerulonephritis in certain strains of mice and rats. Secondly, mercury exposure impairs cell-mediated and humoral immunity by affecting Thl and Th2 responses, which in turn impairs the body s ability to effectively... 

Hua J, Pelletier L, Berlin M, Druet P. Autoimmune glomerulonephritis induced by mercury vapour exposure in the Brown Norway rat.Toxicology 1993 79 119-29. 

Langworth et al. 1992b). There is limited information in humans that suggests that certain individuals may develop an autoimmune response when exposed to mercury. Deposition of IgG and complement C3 have been observed in the glomeruli of two workers with mercury-induced proteinuria (Tubbs et al. 

Antilaminin antibodies induced by mercuric chloride have been demonstrated to be detrimental to the development of cultured rat embryos (Chambers and Klein 1993). Based upon that observation, those authors suggested that it might be possible for an autoimmune disease induced by a substance such as mercury at an early age to persist into later life, acting as a teratogen independent of both dose-response relationships and time of exposure, but that possibility remains to be experimentally demonstrated. 

Pollard, KM Scripps Research Institute San Diego, CA Mercury induced autoimmunity. NIEHS... 

Bigazzi, PE University of Connecticut Farmington, CT Immune effects of metals-mercury-induced autoimmune disease. NIEHS... 

Bigazzi PE. 1992. Lessons from animal models The scope of mercury-induced autoimmunity. Clin Immunol Immunopathol 65(2) 81-84. 

Castedo M, Pelletier L, Rossert J,et al. 1993. Mercury-induced autoreactive anti-class II T cell line protects from experimental autoimmune encephalomyelitis by the bias of CD 8 + Antiergotypic cells in Lewis rats. J Exp Med 177 881-889. 

Dubey C, Bellon B, Kuhn J, et al. 1991b. Increase of a IA expression on B cells during the course of mercury-induced autoimmune disease in Brown Norway rats. In Bach PH, et al., eds. Nephrotoxicity mechanisms, early diagnosis, and therapeutic management. Fourth International Symposium on Nephrotoxicity. New York, NY Marcel Dekker, Inc., 397-400. 

Hirszel P, Michaelson JH, Dodge K, et al. 1985. Mercury-induced autoimmune glomerulonephritis in inbred rats—part II. Immunohistopathology, histopathology and effects of prostaglandin administration. Surv Synth Pathol Res 4 412-422. 

Kosuda LL, Greiner DL, Bigazzi PE. 1993. Mercury-induced renal autoimmunity changes in rt6+ T-lymphocytes of susceptible and resistant rats. Environ Health Perspectives 101(2) 178-185. 

Kosuda LL, Hosseinzadeh H, Greiner DL, et al. 1994. Role of rt6+ T lymphocytes in mercury-induced renal autoimmunity experimental manipulations of "susceptible" and "resistant" rats. J Toxicol Environ Health 42(3) 303-321. 

Pelletier L, Pasquier R, Hirsch F, et al. 1986. Autoreactive T cells in mercury-induced autoimmune disease in vitro demonstration. J Immunol 137 2548-2554... 

Pelletier L, Rossert J, Pasquier R, et al. 1990. Role of CD8+ cells in mercury-induced autoimmunity or immunosuppression in the rat. Scand J Immunol 31 65-74. 

Bagenstose, L.M., P. Salgame and M. Monesteir. IL-12 down-regulates autoantibody production in mercury-induced autoimmunity. J. Immunol. 160 1612-1617, 1998. 

Hu, H., G. Moller, and M. Ahedi-Valugerdi. 1999. Mechanism of mercury-induced autoimmunity Both T helper 1- and T helper 2-type responses are involved. Immunology 96(3) 348-57. 

It is notable that cadmium as well as mercury and gold can initiate or aggravate autoimmune manifestations in normal or autoimmune-prone animals, respectively. It would seem likely that these heavy metals have the same effects on humans, presumably by a similar mechanism. Autoimmune manifestations induced by heavy metals include lupus-type nephritis, autoimmune haemolytic anaemia, and skin diseases, such as pemphigus and scleroderma-like lesion. Some manifestations of immune-mediated nephritis and elevation of circulating autoantibodies have been noted in case-studies of persons exposed to gold and cadmium as well as mercury (Ohsawa, 1993 Bigazzi, 1994, 1999). 

Rodent susceptibility to the systemic autoimmunity induced by mercury(II) chloride is genetically controlled (see chapter 7). Both MHC class II genes and non-MHC genes determine responsiveness (Hultman et al., 1996 Hanley et al., 1998 Schuppe et al., 1998 Abedi-Valugerdi Moller, 2000 Hultman Nielsen, 2001). The induction and development of autoimmune responses in susceptible strains vary across species. Rats become resistant to mercury-induced autoimmunity after a subsequent challenge, whereas mice do not show resistance to subsequent mercury exposures (see also chapter 10). 

Autoimmune-like phenomena in Brown Norway rats induced by mercuiy(II) chloride peak around day 10 after the last of five subcutaneous injections. After 20 days, immune alterations are mostly at control level, and the kidney effects (e.g. proteinuria) are clearly less than on day 10 (Aten et al., 1988). In addition, low-dose pretreatment of Brown Norway rats with mercuiy(II) chloride prevents development of adverse immunity (Szeto et al., 1999), and neonatal injection of mercury(II) chloride in Brown Norway rats renders them tolerant to mercury-induced (but not gold-induced) autoimmune phenomena (Field et al., 2000). These phenomena, transience of autoimmune effects as well as low-dose protection, are shown to be due at least in part to the development of regulatory immune cells. In the case of mercury(II) chloride, these cells have been identified as either IFN-y-producing CD8+CD45RC high regulatory T cells (Pelletier et al., 1990 Mathieson et al., 1991 Szeto et al., 1999 Field et al., 2003) or RT6.2+ T cells (Kosuda et al., 1994). In view of this, it is relevant to note that Lewis rats that produce predominantly CD8+ regulatory T cells ( suppressor T cells) in response to mercury(II) chloride are resistant to mercury-induced autoimmunity and instead display a polyclonal immunosuppressive response (Pelletier et al., 1987). Based on these differences in strain sensitivity, it is clear that susceptibility to mercury-induced autoimmune effects is dependent on MHC class II haplo-type (Aten et al., 1991). 

Abedi-Valugerdi M Mailer G (2000) Contribution of H-2 and non-H-2 genes in the control of mercury-induced autoimmunity. Int Immunol, 12(10) 1425-1430. 

Bagenstose LM, Salgame P, Monestier M (1998a) Mercury-induced autoimmunity in the absence of IL-4. Clin Exp Immunol, 114 9-12. 

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