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International Immunology, Vol. 11, No. 4, 605-615, April 1999
© 1999 Japanese Society for Immunology

Mercury-induced anti-nucleolar autoantibodies can transgress the membrane of living cells in vivo and in vitro

Manuchehr Abedi-Valugerdi, Hui Hu and Göran Möller

Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, 10691 Stockholm, Sweden

Correspondence to: M. Abedi-Valugerdi

Treatment with HgCl2 induces a systemic autoimmune disease in certain mice and rats. The major characteristic of this disease in mice with H-2s genotype is the production of anti-nucleolar autoantibodies (ANolA). The exact mechanism(s) for the production and the functional role of mercury-induced ANolA are not known. We have studied the ability of mercury-induced ANolA to enter the living cells in vivo and in vitro. We found that in highly susceptible mice, treatment with mercury induced ANolA capable of localizing in the nucleoli of kidney and liver cells in vivo. No detectable nucleoli localization of ANolA were found in the cells of the heart, stomach, intestine and spleen. Consistent with the in vivo studies, mercury-induced ANolA were also able to enter and translocate in the nucleoli of certain cells in vitro. The highest degree of antibody penetration was found in A-498 cells (a human kidney cell line) followed by 3T3 cells (a mouse fibroblast cell line), whereas the cells of lymphoid origin exhibited a very low degree of antibody penetration. Penetrated ANolA could be recovered from the nucleoli of live 3T3 cells previously treated with ANolA. The in vitro nucleolar translocation by ANolA did not affect the DNA synthesis, but was found to be an active process dependent on time and temperature. Furthermore, pre-treatment of living cells with trypsin markedly inhibited both cell entry and nucleolar accumulation of ANolA. Thus, mercury-induced ANolA have a unique ability to transgress the membrane of certain living cells in vivo and in vitro, and to localize in the nucleoli.

Keywords: anti-nucleolar autoantibodies, fibrillarin, H-2s mice, HgCl2, penetrating autoantibodies

Transmitting editor: C. Martinez-A


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