Deposition of IgA is Associated with Macrophage Influx in the Kidney of Rats

Abstract

In the present study we treated rats with N-nitrosodimethylamine (DMN) or D-galactosamine (GALN) to achieve increased circulating IgA levels in rats. GALN-treated rats showed a six-fold increase in serum IgA levels after the first intraperitoneal (i.p.) injection, whereas a 10-fold increase after a second i.p. injection of GALN was seen. DMN-treated rats showed a three-fold increase in serum IgA levels. No differences were observed in IgG and IgM levels between treated and non-treated rats. Sequential renal biopsies analysed by immunofluroescence exhibited mesangial deposits of IgA with different intensities of C3 deposition. Rats treated with GALN showed more IgA deposition in the kidney than DMN-treated rats. The IgA deposition together with C3 was more prominent in rats treated with GALN than in rats treated with DMN. The deposition of C3 together with IgA was associated with an influx of monocytes as detected by ED-1, an antibody directed against a rat monocyte marker. These studies provide evidence that an increase in serum IgA levels is associated with deposition of IgA in the kidney and that IgA has an inflammatory potential.

An acute model for IgA-mediated glomerular inflammation in rats induced by monoclonal polymeric rat IgA antibodies

“…In addition, recently we showed in an experimental mode! in rats thai mesangial IgA deposition together with C3 was assoeiated with an increased number ofintraglomerular monocytes [14]. Furthermore.…”

Different Elimination of Circulating IgA Immune Complexes in Rat and Guinea Pig

“…Despite normal blood clearance rates and normal values for total hepatic uptake of IgA ICs in patients with IgA nephro pathy [52], defective hepatic IgA IC clearance cannot be ruled out as a cause of this condition. For instance, Stad et al [54] found mesangial deposition of IgA, C3 and an in flux of macrophages in the kidneys of rats treated with the liver-damaging substance D-galactosaminc. Several studies have clearly shown that IgA antibodies can mediate hepatocytic clearance of circulating antigen in mice and rats [24][25][26][27]48], Other studies, including work from our laboratory, have suggested a more important role for the NPCs in the handling of circulating IgA ICs [28][29][30].…”

Prospects and Perspectives on IgA Nephropathy from Animal Models

“…A mutant rat strain with autosomal recessive hyperbilirubinuria similar to the Dubin-Johnson syndrome also develops mesangial proliferative glomerulonephritis that resembles IgAN [119]. In yet another model, two hepatoxins induced glomerular disease with features of secondary IgAN [122]; galactosamine was the more effective agent for inciting the IgAN.…”

“…Given the importance of the liver in clearance of IgA immune complexes from the circulation and in cognizance of the occurrence of secondary IgAN in patients with cirrhosis and other hepatobiliary disease, several models of IgAN secondary to liver injury and/or cholestasis were developed in rats [6,7,9,61,117,[119][120][121][122][123] and mice [8,50]. Severe hepatocellular injury induced by carbon tetrachloride progressed to cirrhosis; affected rats developed IgAN characterized by proteinuria and hematuria, and associated with increased levels of circulating immune complexes and serum IgA [6,7].…”