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Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms
The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153854/ https://www.ncbi.nlm.nih.gov/pubmed/27958278 http://dx.doi.org/10.1038/srep38738 |
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author | Marin Oyarzún, Cecilia P. Carestia, Agostina Lev, Paola R. Glembotsky, Ana C. Castro Ríos, Miguel A. Moiraghi, Beatriz Molinas, Felisa C. Marta, Rosana F. Schattner, Mirta Heller, Paula G. |
author_facet | Marin Oyarzún, Cecilia P. Carestia, Agostina Lev, Paola R. Glembotsky, Ana C. Castro Ríos, Miguel A. Moiraghi, Beatriz Molinas, Felisa C. Marta, Rosana F. Schattner, Mirta Heller, Paula G. |
author_sort | Marin Oyarzún, Cecilia P. |
collection | PubMed |
description | The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production. Elevated circulating nucleosomes were a prominent finding and were higher in patients with advanced disease, which may have potential prognostic implication. Histone-MPO complexes, proposed as specific NET biomarker, were seldomly detected, suggesting NETs may not be the main source of nucleosomes in most patients, whereas their correlation with high LDH points to increased cell turn-over as a plausible origin. Lack of association of nucleosomes or NETs with thrombosis or activation markers does not support their use as predictors of thrombosis although prospective studies in a larger cohort may help define their potential contribution to MPN thrombosis. These results do not provide evidence for relevant in vivo NETosis in MPN patients under steady state conditions, although availability of standardized NET biomarkers may contribute to further research in this field. |
format | Online Article Text |
id | pubmed-5153854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-51538542016-12-28 Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms Marin Oyarzún, Cecilia P. Carestia, Agostina Lev, Paola R. Glembotsky, Ana C. Castro Ríos, Miguel A. Moiraghi, Beatriz Molinas, Felisa C. Marta, Rosana F. Schattner, Mirta Heller, Paula G. Sci Rep Article The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood. We assessed whether neutrophil extracellular traps (NETs), which promote thrombosis, contribute to the procoagulant state in essential thrombocythemia, polycythemia vera and myelofibrosis (MF) patients. Although MPN neutrophils showed increased basal reactive oxygen species (ROS), enhanced NETosis by unstimulated neutrophils was an infrequent finding, whereas PMA-triggered NETosis was impaired, particularly in MF, due to decreased PMA-triggered ROS production. Elevated circulating nucleosomes were a prominent finding and were higher in patients with advanced disease, which may have potential prognostic implication. Histone-MPO complexes, proposed as specific NET biomarker, were seldomly detected, suggesting NETs may not be the main source of nucleosomes in most patients, whereas their correlation with high LDH points to increased cell turn-over as a plausible origin. Lack of association of nucleosomes or NETs with thrombosis or activation markers does not support their use as predictors of thrombosis although prospective studies in a larger cohort may help define their potential contribution to MPN thrombosis. These results do not provide evidence for relevant in vivo NETosis in MPN patients under steady state conditions, although availability of standardized NET biomarkers may contribute to further research in this field. Nature Publishing Group 2016-12-13 /pmc/articles/PMC5153854/ /pubmed/27958278 http://dx.doi.org/10.1038/srep38738 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Marin Oyarzún, Cecilia P. Carestia, Agostina Lev, Paola R. Glembotsky, Ana C. Castro Ríos, Miguel A. Moiraghi, Beatriz Molinas, Felisa C. Marta, Rosana F. Schattner, Mirta Heller, Paula G. Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
title | Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
title_full | Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
title_fullStr | Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
title_full_unstemmed | Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
title_short | Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
title_sort | neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153854/ https://www.ncbi.nlm.nih.gov/pubmed/27958278 http://dx.doi.org/10.1038/srep38738 |
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