Abstract
Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.
Highlights
Maximal and minimal acute inflammatory response (AIRmax and AIRmin) mice were obtained by bi-directional artificial genetic selection for an AIR induced by subcutaneous injection of polyacrylamide beads, a non-antigenic, insoluble and chemically inert substance
BALB/c mice were divided into four groups: control (N = 5), only ovalbumin injections (N = 6), only bile duct ligation (N = 6), and ovalbumin injections with bile duct ligation (N = 5)
Control mice and mice receiving ovalbumin injections did not present any histological changes, but bile duct ligation caused a mesangial expansion in some glomeruli in three of six animals and ovalbumin injections with bile duct ligation increased the intensity of mesangial expansion in three of five animals
Summary
Maximal and minimal acute inflammatory response (AIRmax and AIRmin) mice were obtained by bi-directional artificial genetic selection for an AIR induced by subcutaneous injection of polyacrylamide beads, a non-antigenic, insoluble and chemically inert substance. The initial population subjected to this selection (named F0) [1] is highly polymorphic and was obtained from the interbreeding of eight mouse strains (lineage A, DBA2, P, SWR, CBA, SJL, BALB/ c, and C57BL/6). The phenotype characterizad was the influx of leukocytes and plasma protein into the inflammatory exudate 48 h after polyacrylamide injection. The mice were selected for the ability to recruit polymorphonuclear cells at the site of injury [1,2]. The F0 population presented a predominance of polymorphonuclear cells (71%) and 29% monocytes. In the nineteenth generation (F19), mononuclear cells corresponded to 55% of the cells in the exudate of AIRmin mice and polymorphonuclear cells corresponded to 95% of the cells in the exudate of AIRmax mice [2]
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