Abstract
FTY720, A PROMISING NEW type of immunosuppressive agent, is a synthetic structural analog of myriocin, a metabolite of the ascomycete Isaria Sinclairii. Its chemical structure and mechanism of action are different from those of cyclosporine A (CsA), FK506, and other current immunosuppressants. FTY720 modifies lymphocyte trafficking through alteration of the expression or function of certain adhesion molecules. FTY 720 provokes migration of lymphocytes from the peripheral blood to the secondary lymphoid tissues and, as a consequence, a peripheral lymphocytopenia is observed. We already reported that FTY720 has marked anti-acute rejection properties. We also showed that FTY720 does not block tolerance in a model where an heart alloTx is spontaneously accepted after donor specific blood transfusion. Chronic allograft vasculopathy (CAV) remains a leading cause of graft failure after organ Tx. There are no data available on the effect of FTY720 on CAV. Here we investigated the effect of combined use of FTY720 and CsA on CAV in a rat heart transplantation model.
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