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 hep atic allografts from fully allogeneic ACI(RT1(a))-->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. M ethods, We investigated macrophages expressing inducible nitric oxide synthase in animal group I (receiving isografts), group LI (hepatic al lografts), and group III (hepatic allografts after donor-specific bloo d). Results. Serum nitrite/nitrate, interferon-gamma, and tumor necros is factor-alpha concentrations increased significantly in group II for 7 days after transplantation but were significantly much lower in gro ups I and III. Numbers of macrophages immunostained with an anti-macro phage nitric oxide synthase monoclonal antibody and inducible nitric o xide synthase mRNA levels in liver specimens also were much lower in g roups I and III than in group II. In addition, Northern blot analysis demonstrated abundant interleukin-10 mRNA transcripts in the DST-treat ed hepatic allografts compared to untreated allografts. Double immunos taining 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 i n immunologic unresponsiveness to grafts after donor-specific blood tr ansfusion.