A significant reduction of macrophages expressing inducible nitric oxide synthase in rat hepatic allografts pretreated with donor-specific blood.

BACKGROUND

A single intravenous injection of donor-specific blood (DST) 7 days before transplantation significantly prolongs survival of hepatic allografts from fully allogeneic ACI(RT1a)-->LEW(RT1(1)) rats. The aim of this study was to investigate the kinetics of nitric oxide synthesis by macrophages in rat hepatic allografts treated with DST.

METHODS

We investigated macrophages expressing inducible nitric oxide synthase in animal group I (receiving isografts), group II (hepatic allografts), and group III (hepatic allografts after donor-specific blood).

RESULTS

Serum nitrite/nitrate, interferon-gamma, and tumor necrosis factor-alpha concentrations increased significantly in group II for 7 days after transplantation but were significantly much lower in groups I and III. Numbers of macrophages immunostained with an anti-macrophage nitric oxide synthase monoclonal antibody and inducible nitric oxide synthase mRNA levels in liver specimens also were much lower in groups I and III than in group II. In addition, Northern blot analysis demonstrated abundant interleukin-10 mRNA transcripts in the DST-treated hepatic allografts compared to untreated allografts. Double immunostaining revealed anti-macrophage synthase-containing cells, including both ED1+ and ED2+ cells, in liver and spleen as more numerous in group II.

CONCLUSIONS

Inducible nitric oxide synthase is suppressed in immunologic unresponsiveness to grafts after donor-specific blood transfusion.