title: High dose of antithrombin III induces indefinite survival of fully allogeneic cardiac grafts and generates regulatory cells.
abstract: BACKGROUND
  The authors investigated whether antithrombin III (AT-III) could induce unresponsiveness to alloantigens.
  
  
  METHODS
  CBA mice were given intravenous injection of 50 or 500 U/kg AT-III or control plasma the same day as transplantation of a heart from a C57BL/6 mouse. An adoptive transfer study and mixed leukocyte culture analysis were also performed.
  
  
  RESULTS
  Naive CBA mice rejected C57BL/6 cardiac grafts acutely (median survival time [MST], 9 days). The 50-U/kg dose of AT-III induced a moderate increase in graft survival (MST, 25 days), whereas control mice rejected their graft acutely (MST, 7 days). With the 500-U/kg dose of AT-III, all grafts survived indefinitely (>100 days) and regulatory cells were generated. In vitro, AT-III suppressed proliferation of mixed leukocyte responses and generation of interleukin-2.
  
  
  CONCLUSIONS
  AT-III can be not only an antithrombotic agent but also a strong immunomodulating agent when used at high dose.
authors.affiliation: Department of Surgery, Nihon University, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Aramaki
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Takayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Seigo
authors.initials: S
authors.lastname: Takano
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Shintaro
authors.initials: S
authors.lastname: Shibutani
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Motohide
authors.initials: M
authors.lastname: Shimazu
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Nozomu
authors.initials: N
authors.lastname: Shirasugi
authors.forename: Masanori
authors.initials: M
authors.lastname: Niimi
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D007376:Interleukin-2 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D014184:Transplantation, Homologous
chemical_list: D007376:Interleukin-2; D000990:Antithrombin III