Peroxynitrite formation during rat hepatic allograft rejection

The role of nitric oxide (NO) on tissue injury of hepatic allografts during rejection remains controversial. We investigated inducible nitric oxide sy nthase (iNOS) expression and formation of peroxynitrite in ACI rat liver gr afts implanted in recipients. Animals were divided into four experimental g roups: group I, isografts; group II, untreated hepatic allografts; group II I, allografts treated with FK506; and group IV, allografts pretreated with donor-specific blood transfusion (DST). Serum nitrite/nitrate, interferon-g amma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) concentration s increased significantly in group II rats after transplantation but were s ignificantly lower in groups I, III, and IV. The numbers of macrophages tha t reacted with an antimacrophage iNOS monoclonal antibody as well as iNOS m essenger RNA (mRNA) levels in liver specimens were also much lower in group s I, III, and IV as compared with group II. Immunostaining and Western blot analysis showed prominent tissue nitrotyrosine expression in untreated hep atic allografts, but not in allografts treated with FK506 or donor-specific blood. These results suggest that one of the mechanisms by which productio n of NO results in injury in rat hepatic allografts may be because of its r eaction with superoxide to form peroxynitrite.