| Abstrakt: |
Abstract Background Heterotopic cardiac transplantation in mice was used to determine whether complementary immunomodulation by statins prevents lymphocyte function-associated antigen (LFA)-1-dependent acute allograft rejection in vivo. Method Hearts from BalbC mice were transplanted to the cervical vessels of either C57BL/6, CD11a−/−, CD28−/− or double-deficient animals lacking expression of both LFA-1 and CD28. Results Allografts were rejected at days 7.2 ± 0.7, 9.1 ± 0.6 and 10.3 ± 1.2 in C57BL/6, CD11a−/− and CD28−/− recipients, respectively. In contrast, mean allograft survival time in double-deficient animals was 27.2 ± 2.9 days, indicating that acute allograft rejection in CD28−/− recipients was critically dependent on LFA-1 function. Allograft rejection was not delayed in CD28−/− recipients treated daily with 1 or 40 mg/kg simvastatin, graft survival was 9.6 ± 0.2 and 10.3 ± 0.3 days in these animals. Histology revealed that all rejected allografts uniformly presented with high-grade parenchymal rejection. Conclusion Targeting of both LFA-1 and CD28 may provide efficient inhibition of co-stimulation and thus prolong experimental cardiac allograft survival. Simvastatin is not effective to blunt LFA-1-dependent acute cardiac allograft rejection in CD28−/− mice. Thus, pharmacological antagonism of LFA-1 function by oral treatment with statin compounds has to be considered an unsatisfactory means to improve the outcome after cardiac transplantation. [ABSTRACT FROM AUTHOR] |
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