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Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis
The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504060/ https://www.ncbi.nlm.nih.gov/pubmed/28694452 http://dx.doi.org/10.1038/s41598-017-04773-8 |
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author | Ma, Ruishuang Xie, Rui Yu, Chengyuan Si, Yu Wu, Xiaoming Zhao, Lu Yao, Zhipeng Fang, Shaohong Chen, He Novakovic, Valerie Gao, Chunyan Kou, Junjie Bi, Yayan Thatte, Hemant S. Yu, Bo Yang, Shufen Zhou, Jin Shi, Jialan |
author_facet | Ma, Ruishuang Xie, Rui Yu, Chengyuan Si, Yu Wu, Xiaoming Zhao, Lu Yao, Zhipeng Fang, Shaohong Chen, He Novakovic, Valerie Gao, Chunyan Kou, Junjie Bi, Yayan Thatte, Hemant S. Yu, Bo Yang, Shufen Zhou, Jin Shi, Jialan |
author_sort | Ma, Ruishuang |
collection | PubMed |
description | The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC. |
format | Online Article Text |
id | pubmed-5504060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55040602017-07-12 Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis Ma, Ruishuang Xie, Rui Yu, Chengyuan Si, Yu Wu, Xiaoming Zhao, Lu Yao, Zhipeng Fang, Shaohong Chen, He Novakovic, Valerie Gao, Chunyan Kou, Junjie Bi, Yayan Thatte, Hemant S. Yu, Bo Yang, Shufen Zhou, Jin Shi, Jialan Sci Rep Article The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC. Nature Publishing Group UK 2017-07-10 /pmc/articles/PMC5504060/ /pubmed/28694452 http://dx.doi.org/10.1038/s41598-017-04773-8 Text en © The Author(s) 2017 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 Ma, Ruishuang Xie, Rui Yu, Chengyuan Si, Yu Wu, Xiaoming Zhao, Lu Yao, Zhipeng Fang, Shaohong Chen, He Novakovic, Valerie Gao, Chunyan Kou, Junjie Bi, Yayan Thatte, Hemant S. Yu, Bo Yang, Shufen Zhou, Jin Shi, Jialan Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
title | Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
title_full | Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
title_fullStr | Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
title_full_unstemmed | Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
title_short | Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
title_sort | phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504060/ https://www.ncbi.nlm.nih.gov/pubmed/28694452 http://dx.doi.org/10.1038/s41598-017-04773-8 |
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