Experimental Goodpasture's syndrome in Wistar-Kyoto rats immunized with 3 chain of type IV collagen

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作者：

MauroAa，RahuramKaur，DanaCorna，NaooYamauch，RorMcCusky，yHudson，usppAndrs，CaraZoja，usppRmuzz

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摘要：

Experimental Goodpasture's syndrome in Wistar-Kyoto rats immunized with 3 chain of type IV collagen.BackgroundGlomerulonephritis and lung hemorrhage of autoimmune Goodpasture syndrome develop due to immune reactions against epitope(s) of the non-collagenous (NC1) domain of 3-chain of type IV collagen [3(IV) NC1]. Whether thymic mechanisms have a role in the loss of tolerance to the Goodpasture epitope has not been established. We studied the renal and pulmonary effects of immunization with different forms (monomer, dimer, or hexamer) of 3(IV) NC1 collagen in Wistar-Kyoto (WKY) rats, and assessed whether the intrathymic inoculation of the antigen may protect against anti-GBM disease.MethodsWKY rats were immunized with bovine 3(IV) monomer, dimer, or hexamer, or with 3(IV) NC1 synthetic peptide. Renal function, kidney and lung immunohistology, and circulating and tissue bound antibodies to type IV collagen chains were analyzed. Effects of intrathymic inoculation of antigen on subsequent disease induction were analyzed in WKY rats given 3(IV) NC1 dimer or GBM preparation intrathymically 48 hours before immunization.ResultsProteinuria, linear IgG deposition in GBM, and crescentic glomerulonephritis developed in WKY rats immunized with 3(IV) NC1 dimer or hexamer. Lesions were dose-dependent upon injections of 10 to 100 g dimer. The 3(IV) NC1 monomer induced less severe proteinuria and no crescents. Pulmonary hemorrhage was detectable in 35% of rats immunized with 25 to 100 g 3(IV) NC1 dimer; 3(IV) synthetic peptide (36 carboxyl terminal) did not induce disease. Rats injected intrathymically with up to 100 g 3(IV) NC1 dimer or with GBM 48 hours before immunization were not protected against subsequent development of proteinuria and glomerulonephritis.ConclusionsThese findings document that glomerulonephritis and lung hemorrhage can be elicited in WKY rats by immunization with 3(IV) NC1. Failure of the intrathymic inoculation of antigen to prevent disease suggests that immunological tolerance cannot be achieved by this intervention, in contrast to other autoimmune conditions, and may imply independent roles for cellular and humoral nephritogenic pathways in anti-GBM nephritis.

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关键词：

extracellular matrix dendritic cell thymocyte GBM 3(IV) NC1 peptide lung hemorrhage glomerulonephritis anti-GBM disease

DOI：

10.1046/j.1523-1755.1998.00153.x

被引量：

115

年份：

1998