Deoxyspergualin delays xenograft rejection in the guinea pig-to-C6-deficient rat heart transplantation model.
This study aimed to investigate the effects of 15-deoxyspergualin (DSG), tacrolimus (FK 506) and cyclosporin A (CyA), alone or in combination, on delayed xenograft rejection (DXR). We used the guinea-pig-to-C6-deficient (C6-)-PVG-rat heart transplantation model, since in this strain combination, hyperacute rejection is avoided. In C6- control rats, the guinea pig xenografts survived for 39.2 +/- 6.3 h (mean +/- SD). Splenectomy alone resulted in a xenograft survival of 71.8 +/- 7.8 h, but the addition of CyA or FK 506 did not further improve graft survival (73.6 +/- 3.0 h and 72.0 +/- 17.6 h, respectively). In contrast, DSG treatment increased graft survival to a mean of 99.8 +/- 9.2 h. When CyA or FK 506 was combined with DSG, no additional effects were observed (105 +/- 24.3 h and 95.1 +/- 5.6 h, respectively). DSG alone or in combination with FK 506 or CyA resulted in a significant reduction in the serum IgM levels and reduced the deposits of IgM and IgG in rejected grafts. However, all xenografts were still heavily infiltrated by ED1 + macrophages, regardless of the treatment used. Thus, DSG treatment resulted in moderate prolongation of xenograft survival in C6- rats. The effect seems to be related to suppression of xenoreactive antibody production. To prolong xenograft survival further, strategies that inhibit macrophage infiltration seem required.
Wu
G S
GS
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Sweden.
Korsgren
O
O
Wennberg
L
L
Tibell
A
A
D000818:Animals; D000910:Antibodies, Heterophile / Q000096:biosynthesis / Q000097:blood; D003131:Combined Modality Therapy; D003176:Complement C3 / Q000032:analysis; D003183:Complement C6 / Q000172:deficiency* / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control* / Q000601:surgery; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D006168:Guinea Pigs / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D051381:Rats / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013156:Splenectomy; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use; D014183:Transplantation, Heterologous / Q000276:immunology*; D016042:Transplantation, Heterotopic
D000910:Antibodies, Heterophile; D003176:Complement C3; D003183:Complement C6; D006146:Guanidines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C037258:gusperimus; D016559:Tacrolimus