Cargando…
Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia
Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367952/ https://www.ncbi.nlm.nih.gov/pubmed/22679495 http://dx.doi.org/10.1371/journal.pone.0038255 |
_version_ | 1782234891096686592 |
---|---|
author | de Kleijn, Stan Kox, Matthijs Sama, Iziah Edwin Pillay, Janesh van Diepen, Angela Huijnen, Martijn A. van der Hoeven, Johannes G. Ferwerda, Gerben Hermans, Peter W. M. Pickkers, Peter |
author_facet | de Kleijn, Stan Kox, Matthijs Sama, Iziah Edwin Pillay, Janesh van Diepen, Angela Huijnen, Martijn A. van der Hoeven, Johannes G. Ferwerda, Gerben Hermans, Peter W. M. Pickkers, Peter |
author_sort | de Kleijn, Stan |
collection | PubMed |
description | Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have investigated gene transcription during experimental endotoxemia in whole blood and peripheral blood mononuclear cells. However, the gene transcription response of the circulating pool of neutrophils to systemic inflammatory stimulation in vivo is currently unclear. We examined neutrophil gene transcription kinetics in healthy human subjects (n = 4) administered a single dose of endotoxin (LPS, 2 ng/kg iv). In addition, freshly isolated neutrophils were stimulated ex vivo with LPS, TNFα, G-CSF and GM-CSF to identify stimulus-specific gene transcription responses. Whole transcriptome microarray analysis of circulating neutrophils at 2, 4 and 6 hours after LPS infusion revealed activation of inflammatory networks which are involved in signaling of TNFα and IL-1α and IL-1β. The transcriptome profile of inflammatory activated neutrophils in vivo reflects extended survival and regulation of inflammatory responses. These changes in neutrophil transcriptome suggest a combination of early activation of circulating neutrophils by TNFα and G-CSF and a mobilization of young neutrophils from the bone marrow. |
format | Online Article Text |
id | pubmed-3367952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33679522012-06-07 Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia de Kleijn, Stan Kox, Matthijs Sama, Iziah Edwin Pillay, Janesh van Diepen, Angela Huijnen, Martijn A. van der Hoeven, Johannes G. Ferwerda, Gerben Hermans, Peter W. M. Pickkers, Peter PLoS One Research Article Polymorphonuclear cells (neutrophils) play an important role in the systemic inflammatory response syndrome and the development of sepsis. These cells are essential for the defense against microorganisms, but may also cause tissue damage. Therefore, neutrophil numbers and activity are considered to be tightly regulated. Previous studies have investigated gene transcription during experimental endotoxemia in whole blood and peripheral blood mononuclear cells. However, the gene transcription response of the circulating pool of neutrophils to systemic inflammatory stimulation in vivo is currently unclear. We examined neutrophil gene transcription kinetics in healthy human subjects (n = 4) administered a single dose of endotoxin (LPS, 2 ng/kg iv). In addition, freshly isolated neutrophils were stimulated ex vivo with LPS, TNFα, G-CSF and GM-CSF to identify stimulus-specific gene transcription responses. Whole transcriptome microarray analysis of circulating neutrophils at 2, 4 and 6 hours after LPS infusion revealed activation of inflammatory networks which are involved in signaling of TNFα and IL-1α and IL-1β. The transcriptome profile of inflammatory activated neutrophils in vivo reflects extended survival and regulation of inflammatory responses. These changes in neutrophil transcriptome suggest a combination of early activation of circulating neutrophils by TNFα and G-CSF and a mobilization of young neutrophils from the bone marrow. Public Library of Science 2012-06-05 /pmc/articles/PMC3367952/ /pubmed/22679495 http://dx.doi.org/10.1371/journal.pone.0038255 Text en de Kleijn et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article de Kleijn, Stan Kox, Matthijs Sama, Iziah Edwin Pillay, Janesh van Diepen, Angela Huijnen, Martijn A. van der Hoeven, Johannes G. Ferwerda, Gerben Hermans, Peter W. M. Pickkers, Peter Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia |
title | Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia |
title_full | Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia |
title_fullStr | Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia |
title_full_unstemmed | Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia |
title_short | Transcriptome Kinetics of Circulating Neutrophils during Human Experimental Endotoxemia |
title_sort | transcriptome kinetics of circulating neutrophils during human experimental endotoxemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367952/ https://www.ncbi.nlm.nih.gov/pubmed/22679495 http://dx.doi.org/10.1371/journal.pone.0038255 |
work_keys_str_mv | AT dekleijnstan transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT koxmatthijs transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT samaiziahedwin transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT pillayjanesh transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT vandiepenangela transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT huijnenmartijna transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT vanderhoevenjohannesg transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT ferwerdagerben transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT hermanspeterwm transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia AT pickkerspeter transcriptomekineticsofcirculatingneutrophilsduringhumanexperimentalendotoxemia |