Cationic dextran induces mesangioproliferative nephritis in rats independent of glomerular IgA deposition.
BACKGROUND
Dextran-induced mesangioproliferative glomerulonephritis in mice and, as recently reported, in rats is used as a model of IgA nephropathy. The pathogenetic role of the glomerular IgA deposits in this model, however, is unclear since IgG is often deposited in parallel.


METHODS
Lewis rats were immunized with cationic DEAE-dextran. Following this, rats received 5 x/week i.v. injections of 3 mg DEAE-dextran each, from days 20 to 80 and were then followed until day 120.


RESULTS
Rats developed transient proteinuria (range 63-152 mg/24 h) and haematuria on day 80. Renal biopsies obtained at days 60, 80, 100 and 120 showed mild to severe mesangioproliferative changes at days 80 and 100 which did not persist at day 120. Electron-microscopy revealed mesangial immune deposits, signs of endothelial activation and vacuoles in mesangial cells and podocytes. Compared to normal, age-matched controls, in the nephritic rats significant (P < 0.05) increases were noted for glomerular total cellularity, alpha-smooth-muscle actin expression (a marker of activated mesangial cells), monocyte/macrophage counts, and matrix proteins. Using three different antibodies, no evidence of glomerular IgA deposition was detected at any time point. In contrast, glomerular IgG, IgM, C3, and occasional small C5b-9 deposits were present in nephritic rats. Circulating IgG but not IgA anti-dextran antibodies could be demonstrated in nephritic rats.


CONCLUSIONS
The data confirm that mesangioproliferative glomerulonephritis can be induced in rats by immunization and chronic challenge with cationic dextran. Our data also show that in rats glomerular IgG deposition rather than IgA, appears to play an important pathogenetic role in this mesangioproliferative glomerulonephritis model.
Burg
M
M
Division of Nephrology, Medizinische Hochschule, Hannover, Germany.
Gröne
H J
HJ
Koch
K M
KM
Floege
J
J
D000818:Animals; D000906:Antibodies / Q000032:analysis; D002412:Cations; D003637:DEAE-Dextran / Q000276:immunology*; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014556:Urine / Q000737:chemistry
D000906:Antibodies; D002412:Cations; D007070:Immunoglobulin A; D003637:DEAE-Dextran