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Peroxynitrite formation during rat hepatic allograft rejection
Author(s) -
Yamaguchi Yasuo,
Okabe Kazutoshi,
Matsumura Fujio,
Akizuki Eiji,
Matsuda Teishi,
Ohshiro Hajime,
Liang Jian,
Yamada Shinwa,
Mori Katsutaka,
Ogawa Michio
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510290354
Subject(s) - peroxynitrite , nitrotyrosine , nitric oxide , immunostaining , nitric oxide synthase , western blot , transplantation , chemistry , immunology , pathology , immunohistochemistry , medicine , superoxide , biochemistry , enzyme , gene
The role of nitric oxide (NO) on tissue injury of hepatic allografts during rejection remains controversial. We investigated inducible nitric oxide synthase (iNOS) expression and formation of peroxynitrite in ACI rat liver grafts implanted in recipients. Animals were divided into four experimental groups: group I, isografts; group II, untreated hepatic allografts; group III, allografts treated with FK506; and group IV, allografts pretreated with donor‐specific blood transfusion (DST). Serum nitrite/nitrate, interferon‐γ (IFN‐γ), and tumor necrosis factor‐α (TNF‐α) concentrations increased significantly in group II rats after transplantation but were significantly lower in groups I, III, and IV. The numbers of macrophages that reacted with an antimacrophage iNOS monoclonal antibody as well as iNOS messenger RNA (mRNA) levels in liver specimens were also much lower in groups I, III, and IV as compared with group II. Immunostaining and Western blot analysis showed prominent tissue nitrotyrosine expression in untreated hepatic allografts, but not in allografts treated with FK506 or donor‐specific blood. These results suggest that one of the mechanisms by which production of NO results in injury in rat hepatic allografts may be because of its reaction with superoxide to form peroxynitrite.