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

Treatment with HgCl2 induces a systemic autoimmune disease in certain mice and rats. The major characteristic of this disease in mice with H-2(s) geno type is the production of anti-nucleolar autoantibodies (ANolA). The exact mechanism(s) for the production and the functional role of mercury-induced ANoIA are not known, We have studied the ability of mercury-induced ANolA t o enter the living cells in vivo and in vitro, We found that in highly susc eptible mice, treatment with mercury induced ANolA capable of localizing in the nucleoli of kidney and liver cells in vivo, No detectable nucleoli loc alization of ANolA were found in the cells of the heart, stomach, intestine and spleen. Consistent with the in vivo studies, mercury-induced ANolA wer e also able to enter and translocate in the nucleoli of certain cells in vi tro. 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 lin e), whereas the cells of lymphoid origin exhibited a very low degree of ant ibody penetration, Penetrated ANolA could be recovered from the nucleoli of live 3T3 cells previously treated with ANolA. The in vitro nucleolar trans location by ANolA did not affect the DNA synthesis, but was found to be an active process dependent on time and temperature, Furthermore, pre-treatmen t of living cells with trypsin markedly inhibited both cell entry and nucle olar accumulation of ANolA. Thus, mercury-induced ANolA have a unique abili ty to transgress the membrane of certain living cells in vivo and in vitro, and to localize in the nucleoli.