Mercury Induced Antinuclear Antibodies in Mice: Characterization and Correlation with Renal Immune Complex Deposits

Female SJL and Balb/c mice were given subcutaneous injections of 1.6 mg HgCl2/kg body weight every third day for 2, 4, 8, or 12 weeks. Indirect immunofluorescence using HEp-2 cells as substrate showed that SJL mice developed antinuclear antibodies (ANA) with a predominantly nucleolar and a weaker, homogeneous nuclear pattern after 4 weeks treatment. The nucleolar antigen was sensitive to treatment with trypsin and RNAse, but the antibody was not absorbed by calf liver RNA. The antigen responsible for the homogeneous nuclear pattern was sensitive to treatment with trypsin, DNAse, and acid solution, but reconstitution with histones on acid treated substrate did not restore the fluorescence. The corresponding antibody was not absorbed by double-stranded or single-stranded DNA, and the Crithidia luciliae assay was negative. This suggests that the antigen responsible for the homogeneous ANA pattern is a non-histone chromatin protein. No autoantibodies were found in Balb/c mice. Electron dense immune deposits containing IgG and C3 in a mesangial-vascular pattern developed after 4 weeks mercury treatment in SJL and Balb/c mice. Acid eluate from kidneys of SJL mice with immune deposits contained tissue-bound ANA with a strictly anti-nucleolar pattern, showing that such antibodies make up part of the renal immune deposits. No autoantibodies were found in the eluate from Balb/c mice. The findings demonstrate that mercury induces a polyclonal autoantibody response in SJL mice, and suggests a restricted antibody response with unknown specificity in Balb/c mice, in both cases leading to immune complex deposits in the kidneys.