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Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation
BACKGROUND: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms. STUDY DESIGN: We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibit...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035455/ https://www.ncbi.nlm.nih.gov/pubmed/27663514 http://dx.doi.org/10.1186/s12967-016-1013-7 |
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author | Delpech, Pierre-Olivier Thuillier, Raphael SaintYves, Thibault Danion, Jerome Le Pape, Sylvain van Amersfoort, Edwin S. Oortwijn, Beatrijs Blancho, Gilles Hauet, Thierry |
author_facet | Delpech, Pierre-Olivier Thuillier, Raphael SaintYves, Thibault Danion, Jerome Le Pape, Sylvain van Amersfoort, Edwin S. Oortwijn, Beatrijs Blancho, Gilles Hauet, Thierry |
author_sort | Delpech, Pierre-Olivier |
collection | PubMed |
description | BACKGROUND: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms. STUDY DESIGN: We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage. RESULTS: Serum creatinine measurement showed that treated animals recovered glomerular function quicker than the Vehicle group. However, no difference was observed in tubular function recovery, and elevated level of urinary NGal (Neutrophil gelatinase-associated lipocalin) and plasma AST (Aspartate Aminotransferase) were detected, indicating that treatment did not influence IRI-mediated tubular cell necrosis. Regarding chronic graft outcome, rhC1INH significantly prevented fibrosis development and improved function. Immunohistochemistry and western blot showed decreased invasion by macrophages and T lymphocytes, and reduction of epithelial to mesenchymal transition. We determined the effect of treatment on complement activation with immunofluorescence analyses at 30 min post reperfusion, showing an inhibition of C4d deposition and MBL staining in treated animals. CONCLUSIONS: In this model, the inhibition of complement activation by rhC1INH at reperfusion, while not completely counteracting IRI, limited immune system activation, significantly improving graft outcome on the short and long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-1013-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5035455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-50354552016-09-29 Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation Delpech, Pierre-Olivier Thuillier, Raphael SaintYves, Thibault Danion, Jerome Le Pape, Sylvain van Amersfoort, Edwin S. Oortwijn, Beatrijs Blancho, Gilles Hauet, Thierry J Transl Med Research BACKGROUND: Ischemia reperfusion injury (IRI) induced immune response is a critical issue in transplantation. Complement and contact system activation are among its key mechanisms. STUDY DESIGN: We investigated the benefits of pre-reperfusion treatment with recombinant human C1INH (rhC1INH), inhibitor of both complement and contact activation, in a pig model of kidney autotransplantation, subjecting the organ to 60 min warm ischemia prior to 24 h static preservation to maximize damage. RESULTS: Serum creatinine measurement showed that treated animals recovered glomerular function quicker than the Vehicle group. However, no difference was observed in tubular function recovery, and elevated level of urinary NGal (Neutrophil gelatinase-associated lipocalin) and plasma AST (Aspartate Aminotransferase) were detected, indicating that treatment did not influence IRI-mediated tubular cell necrosis. Regarding chronic graft outcome, rhC1INH significantly prevented fibrosis development and improved function. Immunohistochemistry and western blot showed decreased invasion by macrophages and T lymphocytes, and reduction of epithelial to mesenchymal transition. We determined the effect of treatment on complement activation with immunofluorescence analyses at 30 min post reperfusion, showing an inhibition of C4d deposition and MBL staining in treated animals. CONCLUSIONS: In this model, the inhibition of complement activation by rhC1INH at reperfusion, while not completely counteracting IRI, limited immune system activation, significantly improving graft outcome on the short and long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-016-1013-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-09-23 /pmc/articles/PMC5035455/ /pubmed/27663514 http://dx.doi.org/10.1186/s12967-016-1013-7 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Delpech, Pierre-Olivier Thuillier, Raphael SaintYves, Thibault Danion, Jerome Le Pape, Sylvain van Amersfoort, Edwin S. Oortwijn, Beatrijs Blancho, Gilles Hauet, Thierry Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
title | Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
title_full | Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
title_fullStr | Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
title_full_unstemmed | Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
title_short | Inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
title_sort | inhibition of complement improves graft outcome in a pig model of kidney autotransplantation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035455/ https://www.ncbi.nlm.nih.gov/pubmed/27663514 http://dx.doi.org/10.1186/s12967-016-1013-7 |
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