High dose of antithrombin III induces indefinite survival of fully allogeneic cardiac grafts and generates regulatory cells.
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.
Aramaki
Osamu
O
Department of Surgery, Nihon University, Tokyo, Japan.
Takayama
Tadatoshi
T
Yokoyama
Takeshi
T
Takano
Seigo
S
Akiyama
Yoshinobu
Y
Shibutani
Shintaro
S
Matsumoto
Kenji
K
Shimazu
Motohide
M
Kitajima
Masaki
M
Ikeda
Yoshifumi
Y
Shirasugi
Nozomu
N
Niimi
Masanori
M
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
D007376:Interleukin-2; D000990:Antithrombin III