title: Unbalanced expression of ADAMTS13 and von Willebrand factor in mouse endotoxinemia.
abstract: BACKGROUND
  Secondary ADAMTS13 deficiency may occur in septic patients. The expression of ADAMTS13 in mouse endotoxinemia was studied.
  
  
  METHODS
  The blood and mRNA expression levels of ADAMTS13 and von Willebrand factor were measured in lipopolysaccharide-injected mice.
  
  
  RESULTS
  The plasma ADAMTS13 activity in wild-type mice was significantly decreased at 2 h after lipopolysaccharide injection, and this decrease in ADAMTS13 activity preceded the decrease in ADAMTS13 mRNA expression in the liver and continued for 24 h. However, no decreases in the plasma ADAMTS13 activity after lipopolysaccharide injection were observed in mice pretreated with a neutrophil elastase inhibitor or in plasminogen-deficient mice, suggesting that the decrease in ADAMTS13 activity was processed efficiently by the coordinated actions of plasmin and neutrophil elastase. von Willebrand factor mRNA was abundantly expressed in the lung and moderately in the kidney, but showed relatively low expression in the liver without lipopolysaccharide injection. However, von Willebrand factor mRNA expression in the liver was significantly increased after lipopolysaccharide injection and this high expression level continued for 24 h after the injection. The von Willebrand factor and ADAMTS13 mRNA expression levels in these organs changed in the opposite manners following lipopolysaccharide administration. Furthermore, the blood von Willebrand factor level increased after lipopolysaccharide administration, in contrast to the decrease in the blood ADMTS13 level after lipopolysaccharide administration.
  
  
  CONCLUSIONS
  These data suggest that imbalance between the blood von Willebrand factor and ADAMTS13 levels may occur in endotoxinemia, and that this may partly contribute to the thrombotic state associated with endotoxinemia.
authors.affiliation: Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, 329-0498, Japan. mimuro-j@jichi.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Mimuro
authors.forename: Masanori
authors.initials: M
authors.lastname: Niimura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kashiwakura
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiwata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ono
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ohmori
authors.forename: Seiji
authors.initials: S
authors.lastname: Madoiwa
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakata
mesh_terms: D000071120:ADAMTS13 Protein; D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000235:genetics*; D008070:Lipopolysaccharides / Q000633:toxicity; D008666:Metalloendopeptidases / Q000097:blood / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010958:Plasminogen / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014841:von Willebrand Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014841:von Willebrand Factor; D010958:Plasminogen; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein