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Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis
Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microve...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131186/ https://www.ncbi.nlm.nih.gov/pubmed/30201980 http://dx.doi.org/10.1038/s41598-018-31910-8 |
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author | Vardon Bounes, Fanny Mémier, Vincent Marcaud, Marina Jacquemin, Aemilia Hamzeh-Cognasse, Hind Garcia, Cédric Series, Jennifer Sié, Pierre Minville, Vincent Gratacap, Marie-Pierre Payrastre, Bernard |
author_facet | Vardon Bounes, Fanny Mémier, Vincent Marcaud, Marina Jacquemin, Aemilia Hamzeh-Cognasse, Hind Garcia, Cédric Series, Jennifer Sié, Pierre Minville, Vincent Gratacap, Marie-Pierre Payrastre, Bernard |
author_sort | Vardon Bounes, Fanny |
collection | PubMed |
description | Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. Complementary methods are necessary to characterize platelet activation during sepsis as circulating soluble markers and platelet-monocyte aggregates revealed early platelet activation, while surface activation markers were detected at later stage. A microfluidic based ex-vivo thrombosis assay demonstrated that platelets from septic mice have a prothrombotic behavior at shear rate encountered in microvessels. Interestingly, we found that even though phosphoinositide-3-kinase β−deficient platelet mice formed less thrombi in liver microcirculation, peritoneal sepsis activates a platelet alternative pathway to compensate the otherwise mandatory role of this lipid-kinase to form stable thrombi at high shear rate. Platelets are rapidly activated during sepsis. Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis. |
format | Online Article Text |
id | pubmed-6131186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61311862018-09-13 Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis Vardon Bounes, Fanny Mémier, Vincent Marcaud, Marina Jacquemin, Aemilia Hamzeh-Cognasse, Hind Garcia, Cédric Series, Jennifer Sié, Pierre Minville, Vincent Gratacap, Marie-Pierre Payrastre, Bernard Sci Rep Article Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. Complementary methods are necessary to characterize platelet activation during sepsis as circulating soluble markers and platelet-monocyte aggregates revealed early platelet activation, while surface activation markers were detected at later stage. A microfluidic based ex-vivo thrombosis assay demonstrated that platelets from septic mice have a prothrombotic behavior at shear rate encountered in microvessels. Interestingly, we found that even though phosphoinositide-3-kinase β−deficient platelet mice formed less thrombi in liver microcirculation, peritoneal sepsis activates a platelet alternative pathway to compensate the otherwise mandatory role of this lipid-kinase to form stable thrombi at high shear rate. Platelets are rapidly activated during sepsis. Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis. Nature Publishing Group UK 2018-09-10 /pmc/articles/PMC6131186/ /pubmed/30201980 http://dx.doi.org/10.1038/s41598-018-31910-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Vardon Bounes, Fanny Mémier, Vincent Marcaud, Marina Jacquemin, Aemilia Hamzeh-Cognasse, Hind Garcia, Cédric Series, Jennifer Sié, Pierre Minville, Vincent Gratacap, Marie-Pierre Payrastre, Bernard Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
title | Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
title_full | Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
title_fullStr | Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
title_full_unstemmed | Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
title_short | Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
title_sort | platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131186/ https://www.ncbi.nlm.nih.gov/pubmed/30201980 http://dx.doi.org/10.1038/s41598-018-31910-8 |
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