Phenotype and localization of macrophages expressing inducible nitric oxide synthase in rat hepatic allograft rejection
Goto, M.; Yamaguchi, Y.; Ichiguchi, O.; Miyanari, N.; Akizuki, E.; Matsumura, F.; Matsuda, T.; Mori, K.; Ogawa, M.
Transplantation 64(2): 303-310
1997
ISSN/ISBN: 0041-1337 PMID: 9256192 Document Number: 477693
Background: We investigated the phenotype and localization of macrophages expressing inducible nitric oxide synthase (iNOS) in rat hepatic allografts, using double immunostaining with anti-macrophage iNOS (macNOS) and rat anti-macrophage (ED1 or ED2) monoclonal antibodies. Methods: The animals were divided into three experimental groups: group 1, isografts; group 2, untreated hepatic allografts; and group 3, hepatic allografts treated with FK506. Results: Plasma nitrite/nitrate concentrations in group 2 increased on day 3, peaked on day 5, and decreased thereafter. In contrast, the plasma nitrite/nitrate concentrations in group 1 increased slightly on day 3, but decreased gradually thereafter. The plasma concentrations of nitrite/nitrate did not vary in group 3. The peak nitrite/nitrate values in group 2 were significantly greater than those in groups 1 and 3. The number of macNOS+ cells peaked on day 5 in group 2. In contrast, a few macNOS+ cells were seen in the liver grafts of groups 1 and 3. Double immunostaining revealed that the macNOS+ cells consisted of macNOS+ED1+ (80%) and macNOS+ED2+ (40%) in the untreated hepatic allografts on day 5. In addition, a number of macNOS+ cells also were seen in the red pulp of the recipient spleen in the untreated hepatic allografts. Conclusions: These results suggest that the intense iNOS expression by the monocyte/macrophage lineage among the hepatic infiltrates and by the splenic macrophages after transplantation supports a role for nitric oxide in the immunomodulation of allogeneic responses in local and remote organs, and possibly serves as a mediator of cytotoxic graft damage.