Characterization of nephropathy induced by immunization with high molecular weight dextran.
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 the 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.
Pasi
A
A
Medizinische Poliklinik, Ludwig-Maximilians-Universität München, Germany.
Dendorfer
U
U
Holthöfer
H
H
Nelson
P J
PJ
Tazzari
S
S
Armelloni
S
S
Fornasieri
A
A
D'Amico
G
G
Schlöndorff
D
D
D000818:Animals; D018946:Chemokine CCL5 / Q000378:metabolism; D003637:DEAE-Dextran / Q000737:chemistry / Q000276:immunology*; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis / Q000276:immunology; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D008970:Molecular Weight; D011507:Proteinuria / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
D018946:Chemokine CCL5; D007070:Immunoglobulin A; D003637:DEAE-Dextran