
Deoxyspergualin delays xenograft rejection in the guinea pig‐to‐C6‐deficient rat heart transplantation model
Author(s) -
Wu Guosheng S.,
Lars Olle Korsgren,
Wennberg L.,
Tibell Annika
Publication year - 1999
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.1999.tb00768.x
Subject(s) - medicine , guinea pig , transplantation , heart transplantation , tacrolimus , pharmacology , immunology
This study aimed to investigate the effects of 15‐deoxyspergu‐alin (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 EDI + 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.