Immunosuppression with FK506 in rat arterial allografts: fate of allogeneic endothelial cells.

Abstract

This study clarified the efficacy of low-dose FK506 and the possibility of discontinuing the use of FK506. Fresh carotid arteries were allografted from ACI rats to Lewis rats. FK506 (0.2 mg/kg/day) was given intramuscularly from day 3 after transplantation until the rats were killed (group III), or it was given for 4 weeks and then discontinued (group IV). Isogeneic (group I) and allogeneic (group II) models served as untreated control groups. Grafts were harvested on days 0, 1, 3, 7, 14, 21, 28, 70, and 105 after transplantation. Histological evaluation and measurement of the endothelial cell (EC)-covered area were performed by means of scanning electron microscopy. In group I, ECs were denuded immediately after transplantation and subsequently regenerated within 2 weeks. In group II, after denudation and regeneration of ECs, massive leukocyte adhesion and subsequent destruction of regenerated ECs, followed by intimal hyperplasia, were observed. In group III, FK506 suppressed rejection almost completely, without intimal hyperplasia. In group IV, severe rejection and denudation of regenerated intima appeared 2 weeks after the use of FK506 ended. The denudation and regeneration of ECs may play an important role in the process of rejection and graft performance. FK506 proved to be successful in rat arterial allografting, and ECs of donor origin could survive on the allograft as long as FK506 was effective; however, cessation of the use of FK506 resulted in severe destruction of intima. To prevent allograft failure, long-term administration of an immunosuppressant is essential.