Dose-response studies in murine mercury-induced autoimmunity and immune-complex disease.
Female SJL/N mice were given either 5.0, 2.5, 1.25, or 0.625 mg mercuric chloride per liter drinking water (ppm HgCl2). Serum antinucleolar antibodies (ANuA) of the IgG class were seen in mice given at least 1.25 ppm HgCl2 for 10 weeks, a dose which corresponded to a mean renal mercury concentration, as measured with atomic absorption spectrophotometry, of 2.4 +/- 0.43 microgram Hg/g wet weight (ppm Hg; means +/- 1 SD). At a dose of 5.0 ppm HgCl2 all mice showed IgG ANuA with a mean titer of 1:846 and a mean renal mercury concentration of 14.8 +/- 3.9 ppm. Significantly increased titers of granular IgG deposits, corresponding to immune-complex (IC) deposits, developed in the renal mesangium of mice given 5.0 ppm HgCl2. Mice with heavy mesangial IgG deposits showed a mild glomerular endocapillary cell proliferation and widening of the mesangium. Renal vessel wall IgG deposits were found only in mice given 5.0 ppm HgCl2, whereas such deposits were seen in splenic and cardiac arteries of mice receiving 1.25 ppm or more of HgCl2. The renal and splenic mercury concentration was significantly increased in all groups of mercuric chloride-exposed mice and correlated with the dose. We conclude that 10 weeks peroral treatment with mercuric chloride in drinking water is able to elicit autoimmunity and IC disease in genetically homogeneous, mercury-sensitive mice at a body burden similar to that reported in some occupationally exposed humans.
Hultman
P
P
Department of Pathology I, Linköping University, Sweden.
Eneström
S
S
D000284:Administration, Oral; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D015551:Autoimmunity / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007105:Immune Complex Diseases / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D008627:Mercuric Chloride / Q000493:pharmacokinetics / Q000633:toxicity*; D051379:Mice; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution
D000974:Antibodies, Antinuclear; D008627:Mercuric Chloride