title: Establishment of a rat model of thrombosis induced by intravenous injection of anti-phosphatidylserine-prothrombin complex antibody.
abstract: 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 .
  
  
  
  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.
  
  
  
  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.
  
  
  
  We established a rat model of thrombosis induced by i.v. injection of aPS-PT mAb.
authors.affiliation: Graduate School of Health Sciences, Hokkaido University, Sapporo.
authors.forename: Mai
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Dermatology, St Marianna University School of Medicine, Kawasaki.
authors.forename: Tamihiro
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Undergraduate School of Health Sciences.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takashima
authors.affiliation: Graduate School of Health Sciences, Hokkaido University, Sapporo.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nishioka
authors.affiliation: Faculty of Health Sciences.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nishibata
authors.affiliation: Faculty of Health Sciences.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Faculty of Health Sciences.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.affiliation: Faculty of Health Sciences.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D001323:Autoantibodies / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006657:Histones / Q000633:toxicity; D007275:Injections, Intravenous; D010718:Phosphatidylserines / Q000276:immunology* / Q000378:metabolism; D011516:Prothrombin / Q000276:immunology*; D017208:Rats, Wistar; D013927:Thrombosis / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006657:Histones; D010718:Phosphatidylserines; D011516:Prothrombin
keywords: animal model; anti-phosphatidylserine–prothrombin complex antibody; anti-phospholipid syndrome; thrombosis