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A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis
Sepsis is a life-threatening condition that requires urgent care. Thus, the identification of specific and sensitive biomarkers for its early diagnosis and management are of clinical importance. The alarmin prothymosin alpha (proTα) and its decapeptide proTα(100-109) are immunostimulatory peptides r...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564713/ https://www.ncbi.nlm.nih.gov/pubmed/28611290 http://dx.doi.org/10.18632/oncotarget.18149 |
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author | Samara, Pinelopi Miriagou, Vivi Zachariadis, Michael Mavrofrydi, Olga Promponas, Vasilis J. Dedos, Skarlatos G. Papazafiri, Panagiota Kalbacher, Hubert Voelter, Wolfgang Tsitsilonis, Ourania |
author_facet | Samara, Pinelopi Miriagou, Vivi Zachariadis, Michael Mavrofrydi, Olga Promponas, Vasilis J. Dedos, Skarlatos G. Papazafiri, Panagiota Kalbacher, Hubert Voelter, Wolfgang Tsitsilonis, Ourania |
author_sort | Samara, Pinelopi |
collection | PubMed |
description | Sepsis is a life-threatening condition that requires urgent care. Thus, the identification of specific and sensitive biomarkers for its early diagnosis and management are of clinical importance. The alarmin prothymosin alpha (proTα) and its decapeptide proTα(100-109) are immunostimulatory peptides related to cell death. In this study, we generated bacterial models of sepsis in mice using two Klebsiella pneumoniae strains (L-78 and ATCC 43816) and monitored sepsis progression using proTα(100-109) as a biomarker. Serum concentration of proTα(100-109) gradually increased as sepsis progressed in mice infected with L-78, a strain which, unlike ATCC 43816, was phagocytosed by monocytes/macrophages. Analysis of splenocytes from L-78-infected animals revealed that post-infection spleen monocytes/macrophages were gradually driven to caspase-3-mediated apoptosis. These results were verified in vitro in L-78-infected human monocytes/macrophages. Efficient phagocytosis of L-78 by monocytes stimulated their apoptosis and the concentration of proTα(100-109) in culture supernatants increased. Human macrophages strongly phagocytosed L-78, but resisted cell death. This is the first report suggesting that high levels of proTα(100-109) correlate, both in vitro and in vivo, with increased percentages of cell apoptosis. Moreover, we showed that low levels of proTα(100-109) early post-infection likely correlate with sepsis resolution and thus, the decapeptide could eventually serve as an early surrogate biomarker for predicting bacteria-induced sepsis outcome. |
format | Online Article Text |
id | pubmed-5564713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55647132017-08-23 A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis Samara, Pinelopi Miriagou, Vivi Zachariadis, Michael Mavrofrydi, Olga Promponas, Vasilis J. Dedos, Skarlatos G. Papazafiri, Panagiota Kalbacher, Hubert Voelter, Wolfgang Tsitsilonis, Ourania Oncotarget Research Paper: Immunology Sepsis is a life-threatening condition that requires urgent care. Thus, the identification of specific and sensitive biomarkers for its early diagnosis and management are of clinical importance. The alarmin prothymosin alpha (proTα) and its decapeptide proTα(100-109) are immunostimulatory peptides related to cell death. In this study, we generated bacterial models of sepsis in mice using two Klebsiella pneumoniae strains (L-78 and ATCC 43816) and monitored sepsis progression using proTα(100-109) as a biomarker. Serum concentration of proTα(100-109) gradually increased as sepsis progressed in mice infected with L-78, a strain which, unlike ATCC 43816, was phagocytosed by monocytes/macrophages. Analysis of splenocytes from L-78-infected animals revealed that post-infection spleen monocytes/macrophages were gradually driven to caspase-3-mediated apoptosis. These results were verified in vitro in L-78-infected human monocytes/macrophages. Efficient phagocytosis of L-78 by monocytes stimulated their apoptosis and the concentration of proTα(100-109) in culture supernatants increased. Human macrophages strongly phagocytosed L-78, but resisted cell death. This is the first report suggesting that high levels of proTα(100-109) correlate, both in vitro and in vivo, with increased percentages of cell apoptosis. Moreover, we showed that low levels of proTα(100-109) early post-infection likely correlate with sepsis resolution and thus, the decapeptide could eventually serve as an early surrogate biomarker for predicting bacteria-induced sepsis outcome. Impact Journals LLC 2017-05-24 /pmc/articles/PMC5564713/ /pubmed/28611290 http://dx.doi.org/10.18632/oncotarget.18149 Text en Copyright: © 2017 Samara et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper: Immunology Samara, Pinelopi Miriagou, Vivi Zachariadis, Michael Mavrofrydi, Olga Promponas, Vasilis J. Dedos, Skarlatos G. Papazafiri, Panagiota Kalbacher, Hubert Voelter, Wolfgang Tsitsilonis, Ourania A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
title | A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
title_full | A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
title_fullStr | A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
title_full_unstemmed | A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
title_short | A fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
title_sort | fragment of the alarmin prothymosin α as a novel biomarker in murine models of bacteria-induced sepsis |
topic | Research Paper: Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564713/ https://www.ncbi.nlm.nih.gov/pubmed/28611290 http://dx.doi.org/10.18632/oncotarget.18149 |
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