Impaired mesangial clearance of macromolecules in rats with chronic mesangial ferritin-antiferritin immune complex deposition.

The mesangial egress, but not the uptake of radiolabeled aggregated human immunoglobulin G (AHIgG125I) (macromolecular proteins biologically akin to immune complexes), deviated markedly from normal in rats with preexisting ferritin-antiferritin immune complexes in the mesangium. Sprague-Dawley rats, given daily intraperitoneal ferritin, 8 mg. per 100 gm. of body weight, for 6 weeks (Ferritin rats), uniformly developed intense mesangial staining for IgG and C3 by immunofluorescence microscopy but minimal glomerular proliferation by light microscopy. With electron microscopy, ferritin was seen in mesangial channels and also in mesangial cells. These rats had normal serum creatinine, no hematuria or proteinuria. AHIgG125I, 50 mg. per 100 gm of body weight, was given intravenously to control and to Ferritin rats; groups of five control and five Ferritin rats were sacrificed at 2, 4, 8, 16, and 24 hours after injection. AHIgG125I was measured in preparations of isolated glomeruli and compared with simultaneous spleen, liver, and blood levels. At all time intervals, blood levels of > 7 S AHIgG125I were similar in control and Ferritin rats. Initial, 2-hour mesangial uptake of AHIgG125I was similar in control and Ferritin rats. During the 2- to 16-hour interval, the disappearance of AHIgG125I from glomeruli of Ferritin rats was delayed; glomerular AHIgG125I concentration decreased 85 per cent in control but only 38 per cent in Ferritin rats. After the administration of AHIgG125I, hematuria (2 to 3+) developed in 60 per cent of Ferritin rats but not in control rats. These studies suggest that immune complexes of different antigen-antibody systems may influence the kinetics of each other locally, at the glomerular level. This impaired mesangial clearance of immune complexes may favor the development of glomerular injury. The experimental model described may be relevant to some forms of human glomerulonephritis in which mesangial pathology and immunopathology are characteristic, and may explain some of the pathogenetic mechanisms operative in these diseases in man.