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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...

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Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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