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Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis
Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
1998
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212493/ https://www.ncbi.nlm.nih.gov/pubmed/9763614 |
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author | Schiller, Brigitte He, Chun Salant, David J. Lim, Alice Alexander, Jessy J. Quigg, Richard J. |
author_facet | Schiller, Brigitte He, Chun Salant, David J. Lim, Alice Alexander, Jessy J. Quigg, Richard J. |
author_sort | Schiller, Brigitte |
collection | PubMed |
description | Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface. |
format | Text |
id | pubmed-2212493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1998 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22124932008-04-16 Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis Schiller, Brigitte He, Chun Salant, David J. Lim, Alice Alexander, Jessy J. Quigg, Richard J. J Exp Med Articles Crry (complement receptor 1–related protein/gene y) is a key cellular complement regulator in rodents. It is also present in Fx1A, the renal tubular preparation used to immunize rats to induce active Heymann nephritis (HN), a model of membranous nephropathy. We hypothesized that rats immunized with anti-Fx1A develop autoantibodies (auto-Abs) to Crry as well as to the megalin-containing HN antigenic complex, and that anti-Crry Abs promote the development of injury in HN by neutralizing the complement regulatory activity of Crry. Rats immunized with Fx1A lacking Crry remained free of proteinuria and glomerular deposits of C3 during a 10-wk follow-up despite typical granular immunoglobulin (Ig)G deposits in glomeruli. Anti-Fx1A auto-Abs were present in their sera at levels that were not different from sera pooled from proteinuric rats with HN induced with nephritogenic Fx1A. Passive administration of sheep anti-Crry Abs to rats immunized with Crry-deficient Fx1A led to proteinuria and glomerular C3 deposition, which were not seen in such rats injected with preimmune IgG, nor in rats with collagen-induced arthritis injected with anti-Crry IgG. To directly examine the role of Crry in HN, rats were immunized with Crry-deficient Fx1A reconstituted with rCrry. This led to typical HN, with 8 out of 15 rats developing proteinuria within 14 wk. Moreover, the extent of glomerular C3 deposition correlated with proteinuria, and anti-Crry Abs were present in glomerular eluates. Thus, Crry is a key nephritogenic immunogen in Fx1A. Formation of neutralizing auto-Abs to Crry impairs its function, leading to unrestricted complement activation by Abs reactive with the HN antigenic complex on the epithelial cell surface. The Rockefeller University Press 1998-10-05 /pmc/articles/PMC2212493/ /pubmed/9763614 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Schiller, Brigitte He, Chun Salant, David J. Lim, Alice Alexander, Jessy J. Quigg, Richard J. Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis |
title | Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis |
title_full | Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis |
title_fullStr | Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis |
title_full_unstemmed | Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis |
title_short | Inhibition of Complement Regulation Is Key to the Pathogenesis of Active Heymann Nephritis |
title_sort | inhibition of complement regulation is key to the pathogenesis of active heymann nephritis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2212493/ https://www.ncbi.nlm.nih.gov/pubmed/9763614 |
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