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Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection
The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved i...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632260/ https://www.ncbi.nlm.nih.gov/pubmed/34858432 http://dx.doi.org/10.3389/fimmu.2021.772859 |
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author | Kim, Seok-Joo Carestia, Agostina McDonald, Braedon Zucoloto, Amanda Z. Grosjean, Heidi Davis, Rachelle P. Turk, Madison Naumenko, Victor Antoniak, Silvio Mackman, Nigel Abdul-Cader, Mohamed Sarjoon Abdul-Careem, Mohamed Faizal Hollenberg, Morley D. Jenne, Craig N. |
author_facet | Kim, Seok-Joo Carestia, Agostina McDonald, Braedon Zucoloto, Amanda Z. Grosjean, Heidi Davis, Rachelle P. Turk, Madison Naumenko, Victor Antoniak, Silvio Mackman, Nigel Abdul-Cader, Mohamed Sarjoon Abdul-Careem, Mohamed Faizal Hollenberg, Morley D. Jenne, Craig N. |
author_sort | Kim, Seok-Joo |
collection | PubMed |
description | The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified. Using confocal intravital microscopy in a mouse model of IAV infection, we observed profound neutrophil recruitment, platelet aggregation, neutrophil extracellular trap (NET) production and thrombin activation within the lung microvasculature in vivo. Importantly, deficiency or antagonism of the protease-activated receptor 4 (PAR4) reduced platelet aggregation, NET production, and neutrophil recruitment. Critically, inhibition of thrombin or PAR4 protected mice from virus-induced lung tissue damage and edema. Together, these data imply thrombin-stimulated platelets play a critical role in the activation/recruitment of neutrophils, NET release and directly contribute to IAV pathogenesis in the lung. |
format | Online Article Text |
id | pubmed-8632260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86322602021-12-01 Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection Kim, Seok-Joo Carestia, Agostina McDonald, Braedon Zucoloto, Amanda Z. Grosjean, Heidi Davis, Rachelle P. Turk, Madison Naumenko, Victor Antoniak, Silvio Mackman, Nigel Abdul-Cader, Mohamed Sarjoon Abdul-Careem, Mohamed Faizal Hollenberg, Morley D. Jenne, Craig N. Front Immunol Immunology The influenza A virus (IAV) causes a respiratory tract infection with approximately 10% of the population infected by the virus each year. Severe IAV infection is characterized by excessive inflammation and tissue pathology in the lungs. Platelet and neutrophil recruitment to the lung are involved in the pathogenesis of IAV, but the specific mechanisms involved have not been clarified. Using confocal intravital microscopy in a mouse model of IAV infection, we observed profound neutrophil recruitment, platelet aggregation, neutrophil extracellular trap (NET) production and thrombin activation within the lung microvasculature in vivo. Importantly, deficiency or antagonism of the protease-activated receptor 4 (PAR4) reduced platelet aggregation, NET production, and neutrophil recruitment. Critically, inhibition of thrombin or PAR4 protected mice from virus-induced lung tissue damage and edema. Together, these data imply thrombin-stimulated platelets play a critical role in the activation/recruitment of neutrophils, NET release and directly contribute to IAV pathogenesis in the lung. Frontiers Media S.A. 2021-11-11 /pmc/articles/PMC8632260/ /pubmed/34858432 http://dx.doi.org/10.3389/fimmu.2021.772859 Text en Copyright © 2021 Kim, Carestia, McDonald, Zucoloto, Grosjean, Davis, Turk, Naumenko, Antoniak, Mackman, Abdul-Cader, Abdul-Careem, Hollenberg and Jenne https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Kim, Seok-Joo Carestia, Agostina McDonald, Braedon Zucoloto, Amanda Z. Grosjean, Heidi Davis, Rachelle P. Turk, Madison Naumenko, Victor Antoniak, Silvio Mackman, Nigel Abdul-Cader, Mohamed Sarjoon Abdul-Careem, Mohamed Faizal Hollenberg, Morley D. Jenne, Craig N. Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection |
title | Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection |
title_full | Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection |
title_fullStr | Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection |
title_full_unstemmed | Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection |
title_short | Platelet-Mediated NET Release Amplifies Coagulopathy and Drives Lung Pathology During Severe Influenza Infection |
title_sort | platelet-mediated net release amplifies coagulopathy and drives lung pathology during severe influenza infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632260/ https://www.ncbi.nlm.nih.gov/pubmed/34858432 http://dx.doi.org/10.3389/fimmu.2021.772859 |
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