Premium
EXPERIMENTAL ANTI‐GBM GLOMERULONEPHRITIS INDUCED IN RATS BY IMMUNIZATION WITH SYNTHETIC PEPTIDES BASED ON SIX α CHAINS OF HUMAN TYPE IV COLLAGEN
Author(s) -
SUGIHARA KATSUYUKI,
SADO YOSHIKAZU,
NINOMIYA YOSHIFUMI,
WADA HIROYOSHI
Publication year - 1996
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199603)178:3<352::aid-path474>3.0.co;2-7
Subject(s) - glomerulonephritis , immunization , chemistry , pharmacology , medicine , immunology , endocrinology , antibody , kidney
The anti‐glomerular basement membrane (GBM)‐nephritis‐inducing activity of six synthetic peptides having an amino acid sequence consisting of the six α 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 α1 to α6 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 WKY–Crj rats. The number of rats with proteinuria (over 10·0 mg of urinary protein/15 h) and haematuria was 2 with the α3 peptide, 8 with the α4 peptide, and 1 with the α5 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 α4 peptide. A nephritogenic monoclonal antibody against the α4 peptide was established using lymph node cells from a rat injected with the α4 peptide. The results indicate that α4(IV)NC1 is a potent nephritogenic antigen like α3(IV)NC1, which has already been recognized as a primary target antigen in Goodpasture's syndrome.