Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis

Abstract 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 phosphatidy...

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Autores principales:	Ruishuang Ma, Rui Xie, Chengyuan Yu, Yu Si, Xiaoming Wu, Lu Zhao, Zhipeng Yao, Shaohong Fang, He Chen, Valerie Novakovic, Chunyan Gao, Junjie Kou, Yayan Bi, Hemant S. Thatte, Bo Yu, Shufen Yang, Jin Zhou, Jialan Shi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/673a6baefff941909e4a41b156da8de4
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spelling	oai:doaj.org-article:673a6baefff941909e4a41b156da8de42021-12-02T12:32:59ZPhosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis10.1038/s41598-017-04773-82045-2322https://doaj.org/article/673a6baefff941909e4a41b156da8de42017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04773-8https://doaj.org/toc/2045-2322Abstract 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.Ruishuang MaRui XieChengyuan YuYu SiXiaoming WuLu ZhaoZhipeng YaoShaohong FangHe ChenValerie NovakovicChunyan GaoJunjie KouYayan BiHemant S. ThatteBo YuShufen YangJin ZhouJialan ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ruishuang Ma Rui Xie Chengyuan Yu Yu Si Xiaoming Wu Lu Zhao Zhipeng Yao Shaohong Fang He Chen Valerie Novakovic Chunyan Gao Junjie Kou Yayan Bi Hemant S. Thatte Bo Yu Shufen Yang Jin Zhou Jialan Shi Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis
description	Abstract 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	article
author	Ruishuang Ma Rui Xie Chengyuan Yu Yu Si Xiaoming Wu Lu Zhao Zhipeng Yao Shaohong Fang He Chen Valerie Novakovic Chunyan Gao Junjie Kou Yayan Bi Hemant S. Thatte Bo Yu Shufen Yang Jin Zhou Jialan Shi
author_facet	Ruishuang Ma Rui Xie Chengyuan Yu Yu Si Xiaoming Wu Lu Zhao Zhipeng Yao Shaohong Fang He Chen Valerie Novakovic Chunyan Gao Junjie Kou Yayan Bi Hemant S. Thatte Bo Yu Shufen Yang Jin Zhou Jialan Shi
author_sort	Ruishuang Ma
title	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_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_sort	phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/673a6baefff941909e4a41b156da8de4
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Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis

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