Mercury-induced renal immune complex deposits in young (NZB x NZW)F1 mice: characterization of antibodies/autoantibodies.
It is well demonstrated that mercury induces a systemic autoimmune disease in susceptible mouse strains. One of the major characteristics of mercury-induced autoimmune disease in mice is the development of renal immune complex deposits. We have previously shown that continual injection of mercury into young autoimmune prone (NZB x NZW)F1 mice induced an increase in antibody/autoantibody production as well as development of early renal immune complex deposits. In the present study, we characterized the isotype, the specificity and the possible pathogenicity of deposited immunoglobulins in the kidneys of mercury-injected (NZB x NZW)F1 hybrids. We found that young (NZB x NZW)F1 mice injected with mercuric chloride (HgCl2) for 6 weeks developed intense antibody formation of all immunoglobulin isotypes (except for IgG2b) as well as high levels of granular deposits of IgM, IgG1, IgG2a and IgG3 antibodies in the renal mesangium. Increased levels of the same antibody isotypes were also found in the kidney eluate of mercury- but not saline-injected mice. The dominant antibody in the kidney eluate of mercury-injected mice was of IgG1 isotype and found to be directed against double-stranded DNA, collagen, cardiolipin, phosphatidylethanolamine, and the hapten trinitrophenol, but not against nucleolar antigens. Further studies demonstrated that mercury-induced renal immune complex deposits in young (NZB x NZW)F1 mice did not lead to a severe kidney injury. Thus, in response to mercury, young (NZB x NZW)F1 mice develop renal immunoglobulin deposits with an isotype and specificity pattern correlating with that seen in the spleen and in the serum.
Abedi-Valugerdi
M
M
Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Hu
H
H
Möller
G
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D000367:Age Factors; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D007132:Immunoglobulin Isotypes; D007668:Kidney / Q000276:immunology*; D008627:Mercuric Chloride / Q000008:administration & dosage*; D051379:Mice
D000906:Antibodies; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D008627:Mercuric Chloride