Mercuric chloride induces a strong immune activation, but does not accelerate the development of dermal fibrosis in tight skin 1 mice.
In susceptible mice, mercuric chloride induces a systemic autoimmune disease characterized by increased serum levels of immunoglobulin (Ig) G1 and IgE, production of anti-nucleolar autoantibodies (ANolA) and formation of renal IgG deposits. We have previously hypothesized that mercury confers more adverse immunological effects on those mouse strains, which are genetically prone to develop spontaneous autoimmune diseases than on normal strains. In this study, we tested our hypothesis in tight skin 1 (Tsk1/+) mice, a murine model for human scleroderma. As a support for our hypothesis, we observed that in Tsk1/+ mice, B cells were spontaneously hyperactive and that treatment with mercury induced a strong immune/autoimmune response in these mice, but not in their non-Tsk (+/+) littermates. This response was characterized by the formation of high numbers of splenic IgG1, IgG2b and IgG3 antibody-secreting cells, increased serum levels of IgE, production of IgG1 antibodies against single-stranded DNA (ssDNA), trinitrophenol (TNP) as well as thyroglobulin and the development of renal IgG1 deposits. Neither Tsk1/+ mice nor F1 hybrid crosses between this strain, and mercury susceptible B10.S (H-2(s)) were able to produce IgG1-ANolA in response to mercury. Moreover, mercury-induced immune activation in Tsk1/+ was not able to potentiate the progression of skin fibrosis in this strain. Thus, exposure to mercury accelerates the immune dysregulation, but not the development of skin fibrosis in Tsk1/+ mice.
Hansson
M
M
Department of Immunology, The Wenner-Gren Institute, Arrhenius Laboratories for the Natural Sciences, Stockholm University, Stockholm, Sweden.
Abedi-Valugerdi
M
M
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005355:Fibrosis / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects; D007132:Immunoglobulin Isotypes; D007668:Kidney / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008627:Mercuric Chloride / Q000276:immunology* / Q000633:toxicity*; D051379:Mice; D008817:Mice, Mutant Strains; D010851:Picrates / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013954:Thyroglobulin / Q000276:immunology
D001323:Autoantibodies; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D010851:Picrates; D008627:Mercuric Chloride; D013954:Thyroglobulin; C005858:picric acid