Journal Article 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

56 ( 6 )  , pp.1013 - 1018 , 2017-06 , Oxford University Press
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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