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Role of HMGB1 in apoptosis-mediated sepsis lethality
Severe sepsis, a lethal syndrome after infection or injury, is the third leading cause of mortality in the United States. The pathogenesis of severe sepsis is characterized by organ damage and accumulation of apoptotic lymphocytes in the spleen, thymus, and other organs. To examine the potential cau...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118346/ https://www.ncbi.nlm.nih.gov/pubmed/16818669 http://dx.doi.org/10.1084/jem.20052203 |
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author | Qin, Shixin Wang, Haichao Yuan, Renqi Li, Hui Ochani, Mahendar Ochani, Kanta Rosas-Ballina, Mauricio Czura, Chris J. Huston, Jared M. Miller, Ed Lin, Xinchun Sherry, Barbara Kumar, Anjali LaRosa, Greg Newman, Walter Tracey, Kevin J. Yang, Huan |
author_facet | Qin, Shixin Wang, Haichao Yuan, Renqi Li, Hui Ochani, Mahendar Ochani, Kanta Rosas-Ballina, Mauricio Czura, Chris J. Huston, Jared M. Miller, Ed Lin, Xinchun Sherry, Barbara Kumar, Anjali LaRosa, Greg Newman, Walter Tracey, Kevin J. Yang, Huan |
author_sort | Qin, Shixin |
collection | PubMed |
description | Severe sepsis, a lethal syndrome after infection or injury, is the third leading cause of mortality in the United States. The pathogenesis of severe sepsis is characterized by organ damage and accumulation of apoptotic lymphocytes in the spleen, thymus, and other organs. To examine the potential causal relationships of apoptosis to organ damage, we administered Z-VAD-FMK, a broad-spectrum caspase inhibitor, to mice with sepsis. We found that Z-VAD-FMK–treated septic mice had decreased levels of high mobility group box 1 (HMGB1), a critical cytokine mediator of organ damage in severe sepsis, and suppressed apoptosis in the spleen and thymus. In vitro, apoptotic cells activate macrophages to release HMGB1. Monoclonal antibodies against HMGB1 conferred protection against organ damage but did not prevent the accumulation of apoptotic cells in the spleen. Thus, our data indicate that HMGB1 production is downstream of apoptosis on the final common pathway to organ damage in severe sepsis. |
format | Text |
id | pubmed-2118346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21183462007-12-13 Role of HMGB1 in apoptosis-mediated sepsis lethality Qin, Shixin Wang, Haichao Yuan, Renqi Li, Hui Ochani, Mahendar Ochani, Kanta Rosas-Ballina, Mauricio Czura, Chris J. Huston, Jared M. Miller, Ed Lin, Xinchun Sherry, Barbara Kumar, Anjali LaRosa, Greg Newman, Walter Tracey, Kevin J. Yang, Huan J Exp Med Brief Definitive Reports Severe sepsis, a lethal syndrome after infection or injury, is the third leading cause of mortality in the United States. The pathogenesis of severe sepsis is characterized by organ damage and accumulation of apoptotic lymphocytes in the spleen, thymus, and other organs. To examine the potential causal relationships of apoptosis to organ damage, we administered Z-VAD-FMK, a broad-spectrum caspase inhibitor, to mice with sepsis. We found that Z-VAD-FMK–treated septic mice had decreased levels of high mobility group box 1 (HMGB1), a critical cytokine mediator of organ damage in severe sepsis, and suppressed apoptosis in the spleen and thymus. In vitro, apoptotic cells activate macrophages to release HMGB1. Monoclonal antibodies against HMGB1 conferred protection against organ damage but did not prevent the accumulation of apoptotic cells in the spleen. Thus, our data indicate that HMGB1 production is downstream of apoptosis on the final common pathway to organ damage in severe sepsis. The Rockefeller University Press 2006-07-10 /pmc/articles/PMC2118346/ /pubmed/16818669 http://dx.doi.org/10.1084/jem.20052203 Text en Copyright © 2006, 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 | Brief Definitive Reports Qin, Shixin Wang, Haichao Yuan, Renqi Li, Hui Ochani, Mahendar Ochani, Kanta Rosas-Ballina, Mauricio Czura, Chris J. Huston, Jared M. Miller, Ed Lin, Xinchun Sherry, Barbara Kumar, Anjali LaRosa, Greg Newman, Walter Tracey, Kevin J. Yang, Huan Role of HMGB1 in apoptosis-mediated sepsis lethality |
title | Role of HMGB1 in apoptosis-mediated sepsis lethality |
title_full | Role of HMGB1 in apoptosis-mediated sepsis lethality |
title_fullStr | Role of HMGB1 in apoptosis-mediated sepsis lethality |
title_full_unstemmed | Role of HMGB1 in apoptosis-mediated sepsis lethality |
title_short | Role of HMGB1 in apoptosis-mediated sepsis lethality |
title_sort | role of hmgb1 in apoptosis-mediated sepsis lethality |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118346/ https://www.ncbi.nlm.nih.gov/pubmed/16818669 http://dx.doi.org/10.1084/jem.20052203 |
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