EXPERIMENTAL ANTI-GBM GLOMERULONEPHRITIS INDUCED IN RATS BY IMMUNIZATION WITH SYNTHETIC PEPTIDES BASED ON SIX α CHAINS OF HUMAN TYPE IV COLLAGEN
✍ Scribed by SUGIHARA, KATSUYUKI; SADO, YOSHIKAZU; NINOMIYA, YOSHIFUMI; WADA, HIROYOSHI
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 857 KB
- Volume
- 178
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
The anti-glomerular basement membrane (GBM)-nephritis-inducing activity of six synthetic peptides having an amino acid sequence consisting of the six a chains of human type IV collagen was examined by injecting the peptides into rats. The peptides consisted of 27 amino acid residues from the non-collagenous domain (NC1) of the a1 to a6 chains and were non-consensus sequences sandwiched between two consensus sequences near the carboxyl terminus. Each peptide was coupled to keyhole limpet haemocyanin and injected with adjuvant into the footpads of 20 female WKYlNCrj rats. The number of rats with proteinuria (over 10.0 mg of urinary proteinll5 h) and haematuria was 2 with the a3 peptide, 8 with the a4 peptide, and 1 with the a5 peptide. Histological changes seen in the glomeruli were characteristic of those in anti-GBM nephritis. Linear deposition of rat IgG along the GBM was observed in five rats injected with the a4 peptide. A nephritogenic monoclonal antibody against the a4 peptide was established using lymph node cells from a rat injected with the a4 peptide. The results indicate that a4(IV)NCl is a potent nephritogenic antigen like a3(1V)NC1, which has already been recognized as a primary target antigen in Goodpasture's syndrome.
KE\ worn-anti-GBM nephritis;