IMPAIRED MESANGIAL CLEARANCE OF MACROMOLECULES IN RATS WITH CHRONIC MESANGIAL FERRITIN-ANTIFERRITIN IMMUNE-COMPLEX DEPOSITION

  • 1 January 1980
    • journal article
    • research article
    • Vol. 43  (6) , 500-508
Abstract
The mesangial egress, but not the uptake of radiolabeled aggregated human IgG (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 i.p. ferritin, 8 mg per 100 g of body weight, for 6 wk (Ferritin rats), uniformly developed intense mesangial staining for IgG and C[complement component]3 by immunofluorescence microscopy but minimal glomerular proliferation by light microscopy. With EM, 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 g of body weight, was given i.v. to control and to Ferritin rats; groups of 5 control and 5 Ferritin rats were sacrificed at 2, 4, 8, 16 and 24 h 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 h mesangial uptake of AHIgG125I was similar in control and Ferritin rats. During the 2 to 16 h interval, the disappearance of AHIgG125I from Ferritin rat glomeruli was delayed; glomerular AHIgG125I concentration decreased 85% in control but only 38% in Ferritin rats. After the AHIgG125I administration, hematuria (2 to 3+) developed in 60% of Ferritin rats but not in control rats. Apparently 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 glomerular injury development. 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.