Overexpression of heme oxygenase-1 protects allogeneic thyroid grafts from rejection in naive mice.
BACKGROUND
Endocrine allografts are an option for the treatment of endocrine failure.


METHODS
One lobe of the thyroid was transplanted under the kidney capsule.


RESULTS
C57BL/10 (H2(b)) thyroids were rejected in naive CBA (H2(k)) mice within 14 days after transplantation. When mice were treated with anti-CD4 monoclonal antibodies (mAb), all grafts survived for more than 60 days. The first grafts still survived after second C57BL/10 or Balb/c (H2(d)) thyroid grafts that were transplanted into the same recipients were rejected acutely, which suggests that the primary grafts were modified under anti-CD4 mAb treatment. To confirm this hypothesis, C57BL/10 thyroid grafts from anti-CD4 mAb-treated mice were retransplanted. All grafts survived in naive mice; this correlated with the overexpression of heme oxygenase-1 (HO-1) in the grafts. Next, an inhibitor of HO-1 (zinc protoporphyrin) or control compound (copper protoporphyrin) was injected intraperitoneally after transplantation of C57BL/10 thyroid grafts into the primary CBA recipients that had been treated with anti-CD4 mAb. The grafts in mice that had been treated with zinc protoporphyrin, but not copper protoporphyrin, were rejected when retransplanted to naive recipients.


CONCLUSIONS
Overexpression of HO-1 correlated with the protection of fully allogeneic thyroid grafts from rejection when retransplanted into naive recipients.
Niimi
M
M
First Department of Surgery, Teikyo University, Tokyo, Japan.
Takashina
M
M
Takami
H
H
Ikeda
Y
Y
Shatari
T
T
Hamano
K
K
Esato
K
K
Matsumoto
K
K
Kameyama
K
K
Kodaira
S
S
Wood
K J
KJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015704:CD4 Antigens / Q000502:physiology; D003167:Complement Activation; D006084:Graft Rejection / Q000517:prevention & control*; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013961:Thyroid Gland / Q000637:transplantation*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D008565:Membrane Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse