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Complement component 5 promotes lethal thrombosis

Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, t...

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Autores principales: Mizuno, Tomohiro, Yoshioka, Kengo, Mizuno, Masashi, Shimizu, Mie, Nagano, Fumihiko, Okuda, Tomoyuki, Tsuboi, Naotake, Maruyama, Shoichi, Nagamatsu, Tadashi, Imai, Masaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311936/
https://www.ncbi.nlm.nih.gov/pubmed/28205538
http://dx.doi.org/10.1038/srep42714
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author Mizuno, Tomohiro
Yoshioka, Kengo
Mizuno, Masashi
Shimizu, Mie
Nagano, Fumihiko
Okuda, Tomoyuki
Tsuboi, Naotake
Maruyama, Shoichi
Nagamatsu, Tadashi
Imai, Masaki
author_facet Mizuno, Tomohiro
Yoshioka, Kengo
Mizuno, Masashi
Shimizu, Mie
Nagano, Fumihiko
Okuda, Tomoyuki
Tsuboi, Naotake
Maruyama, Shoichi
Nagamatsu, Tadashi
Imai, Masaki
author_sort Mizuno, Tomohiro
collection PubMed
description Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis.
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spelling pubmed-53119362017-02-23 Complement component 5 promotes lethal thrombosis Mizuno, Tomohiro Yoshioka, Kengo Mizuno, Masashi Shimizu, Mie Nagano, Fumihiko Okuda, Tomoyuki Tsuboi, Naotake Maruyama, Shoichi Nagamatsu, Tadashi Imai, Masaki Sci Rep Article Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. Nature Publishing Group 2017-02-16 /pmc/articles/PMC5311936/ /pubmed/28205538 http://dx.doi.org/10.1038/srep42714 Text en Copyright © 2017, 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
Mizuno, Tomohiro
Yoshioka, Kengo
Mizuno, Masashi
Shimizu, Mie
Nagano, Fumihiko
Okuda, Tomoyuki
Tsuboi, Naotake
Maruyama, Shoichi
Nagamatsu, Tadashi
Imai, Masaki
Complement component 5 promotes lethal thrombosis
title Complement component 5 promotes lethal thrombosis
title_full Complement component 5 promotes lethal thrombosis
title_fullStr Complement component 5 promotes lethal thrombosis
title_full_unstemmed Complement component 5 promotes lethal thrombosis
title_short Complement component 5 promotes lethal thrombosis
title_sort complement component 5 promotes lethal thrombosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311936/
https://www.ncbi.nlm.nih.gov/pubmed/28205538
http://dx.doi.org/10.1038/srep42714
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