title: Low doses of mercuric chloride cause the main features of anti-nucleolar autoimmunity in female outbred CFW mice.
abstract: The growth of the influence of anthropogenic factors aimed on the improvement of human life has its side effect, for example, living organisms receive increasing exposure to toxic mercuric compounds. Experimental data show that mercury (Hg) salts are able to induce systemic autoimmunity in rodents. This Hg-induced autoimmune process (HgIA) is characterized by T cell-dependent polyclonal activation of B lymphocytes, increased level of serum immunoglobulin G1 (IgG1) and immunoglobulin E (IgE), production of antinucleolar autoantibodies (ANoA), and immune complex deposition in multiple organs. HgIA in mice is used as a model of human systemic autoimmune disorders. However, the dose of mercuric chloride (HgCl2) usually used in laboratory mice to induce HgIA is above the allowable limit for everyday levels of Hg exposure in humans. So, we decided to determine the lowest dose of HgCl2 that is able to trigger autoimmunity in outbred Carworth Farms Swiss Webster (CFW) mice not genetically prone to HgIA development. The lowest dose (50 µg/kg body weight (b.w.)/week) was chosen to match the World Health Organization provisional weekly tolerable intake of total Hg for humans. We also tested HgCl2 at 500 and 1500 µg/kg b.w./week (6.5- and 2-fold less than usually used for induction of HgIA in mice). We found that even the lowest dose of Hg resulted in a statistically significant increase in serum level of IgG1 after 8 weeks of treatment. HgCl2 in doses 500 and 1500 µg/kg b.w./week resulted in a significant increase in serum level of IgG1 after 4 weeks of treatment, followed by ANoA production. Sera of HgCl2-treated mice stained the regions in which the major autoantigen in HgIA, fibrillarin, was revealed. These results suggest that low doses of Hg are able to induce the main features of HgIA in genetically heterozygous mice, and that humans chronically exposed to low doses of Hg may be at risk of autoimmunity induction regardless of their genetic background.
authors.affiliation: Laboratory of Structural Biochemistry, M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation quality4@rambler.ru.
authors.forename: Alla S
authors.initials: AS
authors.lastname: Arefieva
authors.affiliation: Group of Experimental Biology, M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Alfia G
authors.initials: AG
authors.lastname: Kamaeva
authors.affiliation: Group of Experimental Biology, M.M. Shemyakin-Yu.A. Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russian Federation.
authors.forename: Marina S
authors.initials: MS
authors.lastname: Krasilshchikova
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D034961:Antigens, Nuclear / Q000378:metabolism*; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis; D001324:Autoantigens / Q000378:metabolism; D001327:Autoimmune Diseases / Q000209:etiology*; D015551:Autoimmunity / Q000187:drug effects*; D002466:Cell Nucleolus / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D007074:Immunoglobulin G / Q000032:analysis; D007279:Injections, Subcutaneous; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000633:toxicity*; D008630:Mercury Poisoning / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D002868:Chromosomal Proteins, Non-Histone; D004785:Environmental Pollutants; D007074:Immunoglobulin G; C047458:fibrillarin; D008627:Mercuric Chloride
keywords: Low doses; PTWI; antinucleolar autoantibodies; autoimmune process; mercuric chloride; outbred mice