RGD Reference Report - The role of C5a in the development of thrombotic glomerulonephritis in rats. - Rat Genome Database

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The role of C5a in the development of thrombotic glomerulonephritis in rats.

Authors: Kondo, C  Mizuno, M  Nishikawa, K  Yuzawa, Y  Hotta, N  Matsuo, S 
Citation: Kondo C, etal., Clin Exp Immunol. 2001 May;124(2):323-9.
RGD ID: 1600652
Pubmed: PMID:11422211   (View Abstract at PubMed)
PMCID: PMC1906054   (View Article at PubMed Central)

Thrombus formation is the important pathologic finding observed in glomerulonephritis induced by antiglomerular basement membrane (GBM) antibodies. Although strong deposition of C3 and membrane attack complex (MAC) is observed in this disease, the role of complement has not been fully elucidated. The aim of this work was to investigate the role of complement, especially an anaphylatoxin C5a, in a rat model of thrombotic glomerulonephritis. Rats were first pretreated with subclinical dose of lipopolysaccharide (LPS). Thrombotic glomerulonephritis was then induced by intravenous injection with rabbit antirat GBM (RbAGBM) (Group I). For the evaluation of the role of complement, the soluble complement receptor type 1 (sCR1) (Group II) or the C5a receptor antagonist peptide (C5aR-AP) (Group III) was intravenously administered 30 min before RbAGBM injection. For exploring the role of neutrophils, rats were pretreated with cyclophosphamide before induction of disease (Group IV). All rats were sacrificed at 6 h, and histological examination was performed. Rats in Group I developed severe glomerular thrombosis. Leucocyte accumulation and strong binding of C3 and MAC were observed in the glomeruli. In rats treated with sCR1 (Group II) and C5aR-AP (Group III), both leucocyte accumulation and thrombus formation in the glomeruli were significantly inhibited. C3 and MAC were negative in the glomeruli in Group II rats, while they were strongly observed in Group III. In neutrophil depleted rats (Group IV), there was also deposition of C3 and MAC in the glomeruli but thrombus formation was not observed. These findings indicated that glomerular thrombosis is dependent on the leucocytes, and mediated in part by the anaphylatoxin C5a but not MAC in the present model.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
thrombosis  ISOC5ar1 (Rattus norvegicus)1600652; 1600652associated with Anti-Glomerular Basement Membrane DiseaseRGD 
thrombosis  IMP 1600652associated with Anti-Glomerular Basement Membrane DiseaseRGD 

Objects Annotated

Genes (Rattus norvegicus)
C5ar1  (complement C5a receptor 1)

Genes (Mus musculus)
C5ar1  (complement component 5a receptor 1)

Genes (Homo sapiens)
C5AR1  (complement C5a receptor 1)

Objects referenced in this article
Gene C5 complement C5 Homo sapiens
Gene Hc hemolytic complement Mus musculus
Gene C5 complement C5 Rattus norvegicus

Additional Information