Complement depletion abolishes IgA-mediated glomerular inflammation in rats.
Recently, we developed an acute model for IgA-mediated glomerular inflammation in rats in which it was shown that polymeric (p) but not monomeric (m) IgA-containing immune complexes induce acute glomerular inflammation. The glomerular IgA-mediated inflammation is characterized by the activation of complement (C), the presence of intraglomerular macrophages and proteinuria. In the present study, we investigated the role of C in this IgA-mediated nephritis. Rats were pretreated either with cobra venom factor (CVF) to deplete them of circulating C3 or with phosphate-buffered saline followed by introduction of mesangial IgA deposits. Upon deposition of pIgA in the mesangial area, acute proteinuria was observed only in normocomplementemic rats and not in C-depleted animals. Immunofluorescent analysis revealed deposition of C3 and C9 in a pattern identical to that of IgA in the glomeruli of normal rats. Rats pretreated with CVF displayed clear mesangial deposition of IgA in the absence of C3 and C9. In none of the two groups were C4 deposits seen, indicating activation of C via the alternative pathway. In normocomplementemic animals, deposition of IgA together with C3 was associated with an influx of macrophages at day 2. C-depleted rats receiving pIgA also showed an influx of macrophages at 24 h following CVF administration and 1 and 2 days after IgA injection. However, no proteinuria was seen. To obtain insight into the mechanism of macrophage influx in the CVF-treated rats, we also analyzed the number of intraglomerular macrophages in rats receiving only CVF, without introduction of mesangial IgA deposits.(ABSTRACT TRUNCATED AT 250 WORDS)
Stad
R K
RK
Department of Nephrology, University Hospital Leiden, The Netherlands.
van Gijlswijk-Janssen
D J
DJ
van Es
L A
LA
Daha
M R
MR
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement; D003176:Complement C3 / Q000032:analysis; D003186:Complement C9 / Q000032:analysis; D003165:Complement System Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000276:immunology; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology; D007070:Immunoglobulin A / Q000032:analysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D003176:Complement C3; D003186:Complement C9; D007070:Immunoglobulin A; D003165:Complement System Proteins