Myeloablative irradiation and granulocyte colony-stimulating factor prolong the survival of chimeric limb allografts in a rodent model.
BACKGROUND
Limb allografts consist of different types of tissues with varying antigenicities. One of the key components is the bone marrow. Removal and reconstitution of this tissue may allow better control of limb allograft rejection. The authors evaluated the efficacy of a new protocol for bone marrow removal that uses pretransplant graft irradiation, granulocyte colony-stimulating factor, and temporal FK506, with particular reference to the dose requirement and toxicity of irradiation.


METHODS
In total, 57 whole-limb allotransplants from LacZ transgenic rats to Lewis rats were performed. Graft irradiation with various doses ranging from 250 to 1500 R was administered just before transplantation. Granulocyte colony-stimulating factor was given for 4 days, whereas FK506 was used for 28 days. The level of intra-bone marrow chimerism of the graft was evaluated by semiquantitative polymerase chain reaction.


RESULTS
Rejection-free survival of grafts was increased significantly in groups that received more than 1000 R of pretransplant irradiation and granulocyte colony-stimulating factor, whereas grafts that received less than 500 R of irradiation showed no prolongation in survival. Bone marrow in the myeloablative irradiation groups was quickly reconstituted by recipient-derived cells. In the group treated with 1500 R of irradiation, the graft tissue was damaged and this led to infection of the recipient. In the 1000-R group, two of eight recipients showed rejection-free graft survival of more than 1 year without any immunosuppression.


CONCLUSIONS
The authors study found that removal of allogeneic bone marrow in the limb graft and rapid reconstitution with recipient marrow cells reduced the recipient's immune response. Graft rejection was delayed significantly but not completely prevented.
Muramatsu
Keiichi
K
Yamaguchi, Japan From the Department of Orthopedic Surgery, Yamaguchi University School of Medicine.
Kato
Hidetoyo
H
Yoshida
Yuichiro
Y
Moriya
Atsushi
A
Taguchi
Toshihiko
T
D000818:Animals; D046528:Chimerism / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000528:radiation effects; D006086:Graft vs Host Disease / Q000628:therapy*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006614:Hindlimb / Q000637:transplantation*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D023001:Transplantation Tolerance / Q000187:drug effects / Q000528:radiation effects; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation / Q000379:methods*
D016179:Granulocyte Colony-Stimulating Factor