title: Phenotype and localization of macrophages expressing inducible nitric oxide synthase in rat hepatic allograft rejection.
abstract: 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.
authors.affiliation: Department of Surgery II, Kumamoto University Medical School, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Goto
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: O
authors.initials: O
authors.lastname: Ichiguchi
authors.forename: N
authors.initials: N
authors.lastname: Miyanari
authors.forename: E
authors.initials: E
authors.lastname: Akizuki
authors.forename: F
authors.initials: F
authors.lastname: Matsumura
authors.forename: T
authors.initials: T
authors.lastname: Matsuda
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D004578:Electron Spin Resonance Spectroscopy; D004790:Enzyme Induction; D005784:Gene Amplification; D006084:Graft Rejection / Q000235:genetics / Q000473:pathology; D006085:Graft Survival; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000276:immunology*; D008264:Macrophages / Q000201:enzymology*; D008297:Male; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D009573:Nitrites / Q000097:blood; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D014185:Transplantation, Isogeneic
chemical_list: D000911:Antibodies, Monoclonal; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D012194:RNA-Directed DNA Polymerase