Evidence that donor pretreatment with FK506 has a synergistic effect on graft prolongation in hamster-to-rat heart xenotransplantation.
BACKGROUND
Concordant xenografts are rejected in a different fashion than are discordant xenografts or allografts. We tested the effect of donor pretreatment with the use of FK506 combined with posttransplantation FK506 treatment and splenectomy and analyzed the mechanism of rejection in hamster-to-rat heart xenotransplantation.


METHODS
Heart xenotransplantation from hamster to rat was carried out under immunosuppression with the use of donor pretreatment with FK506, posttransplantation FK506 treatment and splenectomy, followed by complement-dependent cytotoxicity assay, delayed type hypersensitivity test, and histologic analysis.


RESULTS
The cardiac graft survived 3 days without donor pretreatment, whereas it survived 4.8 days with donor pretreatment with FK506 (5 mg/kg for 3 days). The graft survival was synergistically enhanced by donor pretreatment, posttransplantation FK506 therapy, and splenectomy, and the longest survival was 43.6 +/- 7.7 days in the group with donor pretreatment, posttransplantation FK506 therapy for 4 weeks, and splenectomy. Delayed-type hypersensitivity response was suppressed significantly in the donor pretreatment group. The antibody typed by immunoglobulin M was mainly detected in the rat serum with the rejected grafts by complement-dependent cytotoxicity assay. Correlating with this complement-dependent cytotoxicity titer, neutrophil infiltration and vasculitis of the coronary vessels were recognized in the rejected grafts, and the marginal zone of the white pulp expanded in the spleen.


CONCLUSIONS
Donor pretreatment with FK506 combined with posttransplantation FK506 therapy and splenectomy suppresses the outlet antigen, immunoglobulin M production, and lymphocyte activation, thereby prolonging the graft survival in hamster-to-rat heart xenotransplantation.
Hayashi
S
S
Department of Surgery II, Nagoya University School of Medicine, Japan.
Ito
M
M
Yasutomi
M
M
Namii
Y
Y
Yokoyama
I
I
Uchida
K
K
Takagi
H
H
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008647:Mesocricetus; D051381:Rats; D011917:Rats, Inbred Lew; D013156:Splenectomy; D016559:Tacrolimus / Q000494:pharmacology*; D014019:Tissue Donors; D014183:Transplantation, Heterologous
D003165:Complement System Proteins; D016559:Tacrolimus