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Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody

Objective. Recent studies have suggested that aPS-PT antibody is one of the most relevant autoantibodies to APS. This study aimed to demonstrate the pathogenicity of aPS-PT antibody in vivo. Methods. At first, cultured rat vascular endothelial cells (RECs) were exposed to calf thymus-derived histone...

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Autores principales: Yamada, Mai, Kawakami, Tamihiro, Takashima, Kohei, Nishioka, Yusuke, Nishibata, Yuka, Masuda, Sakiko, Yoshida, Shigeru, Tomaru, Utano, Ishizu, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445602/
https://www.ncbi.nlm.nih.gov/pubmed/28073955
http://dx.doi.org/10.1093/rheumatology/kew477
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author Yamada, Mai
Kawakami, Tamihiro
Takashima, Kohei
Nishioka, Yusuke
Nishibata, Yuka
Masuda, Sakiko
Yoshida, Shigeru
Tomaru, Utano
Ishizu, Akihiro
author_facet Yamada, Mai
Kawakami, Tamihiro
Takashima, Kohei
Nishioka, Yusuke
Nishibata, Yuka
Masuda, Sakiko
Yoshida, Shigeru
Tomaru, Utano
Ishizu, Akihiro
author_sort Yamada, Mai
collection PubMed
description Objective. Recent studies have suggested that aPS-PT antibody is one of the most relevant autoantibodies to APS. This study aimed to demonstrate the pathogenicity of aPS-PT antibody in vivo. Methods. At first, cultured rat vascular endothelial cells (RECs) were exposed to calf thymus-derived histones. Two hours later, lactate dehydrogenase release from the RECs and expression of PS on the cell surface were assessed. Next, we administered an i.v. injection of calf thymus-derived histones into Wistar rats (12.5 µg/g weight of 8-week-old female rats), and 2 h later they were given an i.v. injection of aPS-PT mAb (1.25 mg/g weight, n = 6) or an equal dose of rat IgM as controls (n = 5). Three days later, histological examination was conducted. Results. Calf thymus-derived histones (>12.5 µg/ml) could injure RECs in vitro. Simultaneously, annexin V could bind to the RECs; thereby, this result indicated that cell-free histone exposure of vascular endothelial cells induced cell surface expression of PS, which is naturally present inside the plasma membrane. Thrombosis developed with higher frequency in the rats given an i.v. injection of aPS-PT mAb than in controls. Conclusion. We established a rat model of thrombosis induced by i.v. injection of aPS-PT mAb.
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spelling pubmed-54456022017-05-31 Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody Yamada, Mai Kawakami, Tamihiro Takashima, Kohei Nishioka, Yusuke Nishibata, Yuka Masuda, Sakiko Yoshida, Shigeru Tomaru, Utano Ishizu, Akihiro Rheumatology (Oxford) Basic and Translational Science Objective. Recent studies have suggested that aPS-PT antibody is one of the most relevant autoantibodies to APS. This study aimed to demonstrate the pathogenicity of aPS-PT antibody in vivo. Methods. At first, cultured rat vascular endothelial cells (RECs) were exposed to calf thymus-derived histones. Two hours later, lactate dehydrogenase release from the RECs and expression of PS on the cell surface were assessed. Next, we administered an i.v. injection of calf thymus-derived histones into Wistar rats (12.5 µg/g weight of 8-week-old female rats), and 2 h later they were given an i.v. injection of aPS-PT mAb (1.25 mg/g weight, n = 6) or an equal dose of rat IgM as controls (n = 5). Three days later, histological examination was conducted. Results. Calf thymus-derived histones (>12.5 µg/ml) could injure RECs in vitro. Simultaneously, annexin V could bind to the RECs; thereby, this result indicated that cell-free histone exposure of vascular endothelial cells induced cell surface expression of PS, which is naturally present inside the plasma membrane. Thrombosis developed with higher frequency in the rats given an i.v. injection of aPS-PT mAb than in controls. Conclusion. We established a rat model of thrombosis induced by i.v. injection of aPS-PT mAb. Oxford University Press 2017-06 2017-01-10 /pmc/articles/PMC5445602/ /pubmed/28073955 http://dx.doi.org/10.1093/rheumatology/kew477 Text en © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Basic and Translational Science
Yamada, Mai
Kawakami, Tamihiro
Takashima, Kohei
Nishioka, Yusuke
Nishibata, Yuka
Masuda, Sakiko
Yoshida, Shigeru
Tomaru, Utano
Ishizu, Akihiro
Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
title Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
title_full Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
title_fullStr Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
title_full_unstemmed Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
title_short Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
title_sort establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine–prothrombin complex antibody
topic Basic and Translational Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445602/
https://www.ncbi.nlm.nih.gov/pubmed/28073955
http://dx.doi.org/10.1093/rheumatology/kew477
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