Defective hepatic handling of IgA immune aggregates by mice with experimental IgA nephropathy.
In an experimental model of IgA nephropathy induced in mice by chronic immunization with dextran, we tested the hypothesis that a defect in the hepatic handling of IgA could be an important determinant in the deposition of IgA in the mesangium. In mice injected with 1-16 doses of 1 mg of dextran (after a preimmunization period of 21 days) the blood clearance of IgA immune aggregates was significantly delayed in relation to control animals, becoming normal at 24 injections. This alteration seems specific since the clearance of IgG aggregates was normal. The percentage of isolated hepatocytes with Fc receptors for IgA decreased significantly over the whole period of dextran immunization. The binding rate of 125I-IgA aggregates to hepatocytes of mice with 24 dextran injections was twice lower than that of control animals. By contrast, the percentage of Kupffer cells with IgA receptors increased over ensuing dextran injections. A progressive increase in the IgA blood levels and in the percentage of mice with mesangial IgA deposits was seen along the period of study. At 24 injections most animals presented moderate to intense mesangial proliferation and abundant electron-dense deposits. On the whole, these data suggest that the early impairment in the liver IgA clearance capacity observed in these animals could facilitate the presence of circulating immune complexes (IC) and their deposition in the mesangium. The increase in serum IgA, seen thereafter, together with the normalization of the IgA clearance capacity, suggest that other pathophysiological mechanism(s) (e.g. in situ IC formation or IgA polymers deposition) must also be involved in this model of experimental IgA nephropathy.
Department of Nephrology, Fundación Jiménez Diaz, Universidad Autónoma, Madrid, Spain.
E
E
González
J
J
González-Cabrero
J
J
Egido
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D007070:Immunoglobulin A / Q000378:metabolism*; D007728:Kupffer Cells / Q000276:immunology; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000032:analysis
D000936:Antigen-Antibody Complex; C045281:IgA receptor; D007070:Immunoglobulin A; D011961:Receptors, Fc; D011971:Receptors, Immunologic