Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice.
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.
Kurihara
R S
RS
Laboratório de Fisiopatologia Renal, Faculdade de Medicina, Universidade de São Paulo, Rua Agostinho Cretella 58, 05337-040 São Paulo, SP, Brazil. roshara@uol.com.br
Yokoo
M
M
Domingues
W V
WV
Cabrera
W H
WH
Ribeiro
O G
OG
Ibañez
O M
OM
Malheiros
D A
DA
Barros
R T
RT
de Almeida Prado
E B
EB
D000208:Acute Disease; D000210:Acute-Phase Reaction / Q000276:immunology / Q000473:pathology; D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology* / Q000502:physiology; D013045:Species Specificity
D018932:Chemokine CCL2