Accelerated glomerulosclerosis in diabetic rats with immune complex injury.
Immune complex-mediated injury has been postulated to contribute to diabetic microangiopathy. To test this hypothesis, immune complex disease was induced in both insulin-deficient (I-) and insulin-treated (I+) rats with streptozocin-induced diabetes mellitus (DM), and the rats were compared with their respective controls. Heymann nephritis (HN), an animal model of membranous nephropathy, was induced in rats by immunization with proximal renal tubular brush border antigen. In addition to the homogeneous mesangial deposits of IgG that developed in diabetic rats, diabetic rats with immune injury also developed immune deposits of IgG and tubular antigen. Diabetic animals with Heymann nephritis developed more intense granular mesangial and capillary wall immune deposits, detected by immunofluorescence (ranked-sums test, P = .002) and electron microscopy. Mesangial immune deposits were associated with mesangial hypercellularity, determined by counting nuclei per glomerular cross section. Diabetic animals with immune injury had an increased number of nuclei (DM, I-, HN: 70 +/- 4; DM, I+, HN: 65 +/- 3) compared with animals with only Heymann nephritis (55 +/- 4) or only diabetes [DM, I-: 52 +/- 4; DM, I+: 54 +/- 3 (mean +/- SE); P less than .05, ANOVA]. An increase in the accumulation of mesangial matrix in diabetic animals with Heymann nephritis was also apparent by light microscopy and immunofluorescence staining of the mesangium for fibronectin. Insulin treatment and control of hyperglycemia did not prevent the development of these changes. Animals with only Heymann nephritis had lesser amounts of immune deposits, which were limited to the subepithelial space and not associated with structural alterations of the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)
Abrass
C K
CK
Department of Medicine, Veterans Administration Medical Center, Seattle, WA 98108.
Cohen
A H
AH
D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D007328:Insulin / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew
D007328:Insulin