Cargando…
The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration
Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high...
Autores principales: | , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2003
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194207/ https://www.ncbi.nlm.nih.gov/pubmed/12975457 http://dx.doi.org/10.1084/jem.20030374 |
_version_ | 1782147650851700736 |
---|---|
author | Strey, Christoph W. Markiewski, Maciej Mastellos, Dimitrios Tudoran, Ruxandra Spruce, Lynn A. Greenbaum, Linda E. Lambris, John D. |
author_facet | Strey, Christoph W. Markiewski, Maciej Mastellos, Dimitrios Tudoran, Ruxandra Spruce, Lynn A. Greenbaum, Linda E. Lambris, John D. |
author_sort | Strey, Christoph W. |
collection | PubMed |
description | Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFα induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor–κB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration. |
format | Text |
id | pubmed-2194207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21942072008-04-11 The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration Strey, Christoph W. Markiewski, Maciej Mastellos, Dimitrios Tudoran, Ruxandra Spruce, Lynn A. Greenbaum, Linda E. Lambris, John D. J Exp Med Article Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFα induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor–κB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration. The Rockefeller University Press 2003-09-15 /pmc/articles/PMC2194207/ /pubmed/12975457 http://dx.doi.org/10.1084/jem.20030374 Text en Copyright © 2003, The Rockefeller University Press 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 | Article Strey, Christoph W. Markiewski, Maciej Mastellos, Dimitrios Tudoran, Ruxandra Spruce, Lynn A. Greenbaum, Linda E. Lambris, John D. The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration |
title | The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration |
title_full | The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration |
title_fullStr | The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration |
title_full_unstemmed | The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration |
title_short | The Proinflammatory Mediators C3a and C5a Are Essential for Liver Regeneration |
title_sort | proinflammatory mediators c3a and c5a are essential for liver regeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194207/ https://www.ncbi.nlm.nih.gov/pubmed/12975457 http://dx.doi.org/10.1084/jem.20030374 |
work_keys_str_mv | AT streychristophw theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT markiewskimaciej theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT mastellosdimitrios theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT tudoranruxandra theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT sprucelynna theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT greenbaumlindae theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT lambrisjohnd theproinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT streychristophw proinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT markiewskimaciej proinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT mastellosdimitrios proinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT tudoranruxandra proinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT sprucelynna proinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT greenbaumlindae proinflammatorymediatorsc3aandc5aareessentialforliverregeneration AT lambrisjohnd proinflammatorymediatorsc3aandc5aareessentialforliverregeneration |