Nephrology Dialysis Transplantation, Vol 12, Issue 9 1849-1855, Copyright © 1997 by Oxford University Press
A Pasi, U Dendorfer, H Holthofer, P Nelson, S Tazzari, S Armelloni, A Fornasieri, G D'Amico and D Schlondorff
Background. Injection of DEAE dextran into Lewis rats
can produce proteinuria and has been reported as a model of IgA
nephropathy. Methods. Cationic diethyl aminoethyl
(DEAE) dextran of molecular weight 500 KDa was injected into male Lewis
rats. After a pre-immunization period of 3 weeks, the animals were divided
into two groups: group 1 (n=14) received daily i.v. injections of 3.5 mg of
antigen, group 2 (n=14) was injected with 1.5 mg three times per week for a
total period of 6 weeks. I.v. treatment was initiated with gradually
increasing doses of DEAE dextran in both groups for 1 week, after which the
maintenance dose was reached. Results. We observed the
appearance of proteinuria in a nephrotic range after 5 weeks of i.v.
injections in group 1 (urinary excretion: 332±83 mg/24 h,
controls: 53±14 mg/24 h). In group 2, the proteinuria was almost
equal to protein excretion of healthy rats of the same weight
(67±20 mg/24 h). The serum and urine creatinine were normal. By
light microscopy of kidney biopsies, the presence of focal and segmental
proliferation of mesangial cells after 6 weeks of i.v. injections was
identified. Immunohistochemistry revealed no deposition of IgA, IgM, IgG,
or C3. Using anti-ED1 antibodies, there was no evidence of interstitial
infiltration of monocytes/macrophages after 6 weeks of i.v. injections.
Staining for proliferating cell nuclear antigen (PCNA) did not show the
presence of proliferating cells either in glomeruli or in the interstitium.
Staining with FITC-WGA lectin revealed focal and segmental loss of the
negative charge in the capillary wall. By electron microscopy there was
deposition of dextran in the basal membrane and segmental and focal damage
of the podocyte foot processes. As the chemokine RANTES may be involved in
glomerular injury, we examined the kidneys of proteinuric and
non-proteinuric rats for the presence of RANTES. By indirect
immunofluorescence only the proteinuric rats showed RANTES deposition in
mesangium. Conclusions. Injection of rats with DEAE
dextran leads to dose-dependent proteinuria without deposition of immune
complexes but with podocyte damage. This is associated with local
expression of the chemokine RANTES which may play a role in proteinuria of
glomerular disease. Keywords: glomerulonephritis; IgA
nephropathy; rats; dextran
ORIGINAL ARTICLES
Characterization of nephropathy induced by immunization with high molecular weight dextran
Medizinische Poliklinik, Ludwig-Maximilians-Universitat Munchen, Munchen, Germany; Divisione di Nefrologia, Ospedale San Carlo Borromeo, Milano, Italy; Dipartimento di Anatomia, Universita di Milano, Italy; Corresponding author at: Medizinische Poliklinik, Klinikum Innenstadt der Universitat Munchen, Peettenkoferstrase 8 a, 80336 Munchen, Germany
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