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A genomic storm in critically injured humans
Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global re...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244029/ https://www.ncbi.nlm.nih.gov/pubmed/22110166 http://dx.doi.org/10.1084/jem.20111354 |
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author | Xiao, Wenzhong Mindrinos, Michael N. Seok, Junhee Cuschieri, Joseph Cuenca, Alex G. Gao, Hong Hayden, Douglas L. Hennessy, Laura Moore, Ernest E. Minei, Joseph P. Bankey, Paul E. Johnson, Jeffrey L. Sperry, Jason Nathens, Avery B. Billiar, Timothy R. West, Michael A. Brownstein, Bernard H. Mason, Philip H. Baker, Henry V. Finnerty, Celeste C. Jeschke, Marc G. López, M. Cecilia Klein, Matthew B. Gamelli, Richard L. Gibran, Nicole S. Arnoldo, Brett Xu, Weihong Zhang, Yuping Calvano, Steven E. McDonald-Smith, Grace P. Schoenfeld, David A. Storey, John D. Cobb, J. Perren Warren, H. Shaw Moldawer, Lyle L. Herndon, David N. Lowry, Stephen F. Maier, Ronald V. Davis, Ronald W. Tompkins, Ronald G. |
author_facet | Xiao, Wenzhong Mindrinos, Michael N. Seok, Junhee Cuschieri, Joseph Cuenca, Alex G. Gao, Hong Hayden, Douglas L. Hennessy, Laura Moore, Ernest E. Minei, Joseph P. Bankey, Paul E. Johnson, Jeffrey L. Sperry, Jason Nathens, Avery B. Billiar, Timothy R. West, Michael A. Brownstein, Bernard H. Mason, Philip H. Baker, Henry V. Finnerty, Celeste C. Jeschke, Marc G. López, M. Cecilia Klein, Matthew B. Gamelli, Richard L. Gibran, Nicole S. Arnoldo, Brett Xu, Weihong Zhang, Yuping Calvano, Steven E. McDonald-Smith, Grace P. Schoenfeld, David A. Storey, John D. Cobb, J. Perren Warren, H. Shaw Moldawer, Lyle L. Herndon, David N. Lowry, Stephen F. Maier, Ronald V. Davis, Ronald W. Tompkins, Ronald G. |
author_sort | Xiao, Wenzhong |
collection | PubMed |
description | Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury. |
format | Online Article Text |
id | pubmed-3244029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32440292012-06-19 A genomic storm in critically injured humans Xiao, Wenzhong Mindrinos, Michael N. Seok, Junhee Cuschieri, Joseph Cuenca, Alex G. Gao, Hong Hayden, Douglas L. Hennessy, Laura Moore, Ernest E. Minei, Joseph P. Bankey, Paul E. Johnson, Jeffrey L. Sperry, Jason Nathens, Avery B. Billiar, Timothy R. West, Michael A. Brownstein, Bernard H. Mason, Philip H. Baker, Henry V. Finnerty, Celeste C. Jeschke, Marc G. López, M. Cecilia Klein, Matthew B. Gamelli, Richard L. Gibran, Nicole S. Arnoldo, Brett Xu, Weihong Zhang, Yuping Calvano, Steven E. McDonald-Smith, Grace P. Schoenfeld, David A. Storey, John D. Cobb, J. Perren Warren, H. Shaw Moldawer, Lyle L. Herndon, David N. Lowry, Stephen F. Maier, Ronald V. Davis, Ronald W. Tompkins, Ronald G. J Exp Med Brief Definitive Report Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury. The Rockefeller University Press 2011-12-19 /pmc/articles/PMC3244029/ /pubmed/22110166 http://dx.doi.org/10.1084/jem.20111354 Text en © 2011 Xiao et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Xiao, Wenzhong Mindrinos, Michael N. Seok, Junhee Cuschieri, Joseph Cuenca, Alex G. Gao, Hong Hayden, Douglas L. Hennessy, Laura Moore, Ernest E. Minei, Joseph P. Bankey, Paul E. Johnson, Jeffrey L. Sperry, Jason Nathens, Avery B. Billiar, Timothy R. West, Michael A. Brownstein, Bernard H. Mason, Philip H. Baker, Henry V. Finnerty, Celeste C. Jeschke, Marc G. López, M. Cecilia Klein, Matthew B. Gamelli, Richard L. Gibran, Nicole S. Arnoldo, Brett Xu, Weihong Zhang, Yuping Calvano, Steven E. McDonald-Smith, Grace P. Schoenfeld, David A. Storey, John D. Cobb, J. Perren Warren, H. Shaw Moldawer, Lyle L. Herndon, David N. Lowry, Stephen F. Maier, Ronald V. Davis, Ronald W. Tompkins, Ronald G. A genomic storm in critically injured humans |
title | A genomic storm in critically injured humans |
title_full | A genomic storm in critically injured humans |
title_fullStr | A genomic storm in critically injured humans |
title_full_unstemmed | A genomic storm in critically injured humans |
title_short | A genomic storm in critically injured humans |
title_sort | genomic storm in critically injured humans |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244029/ https://www.ncbi.nlm.nih.gov/pubmed/22110166 http://dx.doi.org/10.1084/jem.20111354 |
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