Time course and cellular localization of inducible nitric oxide synthases expression during cardiac allograft rejection.
Ann Thorac Surg
; 67(3): 716-22, 1999 Mar.
Article
em En
| MEDLINE
| ID: mdl-10215216
ABSTRACT
BACKGROUND:
We have demonstrated that inhibition of inducible nitric oxide synthase (NOS) ameliorated acute cardiac allograft rejection. This study determined the time course and cellular localization of inducible NOS expression during the histologic progression of unmodified acute rat cardiac allograft rejection.METHODS:
Tissue from syngeneic (ACI to ACI) and allogeneic (Lewis to ACI) transplants were harvested on postoperative days 3 through 10 and analyzed for inducible NOS mRNA expression (ribonuclease protection assay), inducible NOS enzyme activity (conversion of L-[3H]arginine to nitric oxide and L-[3H]citrulline), and nitric oxide production (serum nitrite/nitrate levels). Inducible NOS mRNA and protein expression were localized using in situ hybridization and immunohistochemistry.RESULTS:
Inducible NOS mRNA and enzyme activity were expressed in allografts during mild, moderate, and severe acute rejection (postoperative days 4 through 10), but were not detected in normals, isografts, or allografts before histologic changes of mild acute rejection (postoperative day 3). Inducible NOS expression resulted in increased serum nitrite/nitrate levels during mild and moderate rejection (postoperative days 4 through 6). Inducible NOS mRNA and protein expression localized to infiltrating mononuclear inflammatory cells in allograft tissue sections during all stages of rejection but were not detected in allograft parenchymal cells or in normals or isografts.CONCLUSIONS:
Inducible NOS expression and increased nitric oxide production occurred during the early stages of acute rejection, persisted throughout the unmodified rejection process, and localized to infiltrating inflammatory cells but not allograft parenchymal cells during all stages of acute rejection.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Coração
/
Óxido Nítrico Sintase
/
Rejeição de Enxerto
/
Miocárdio
Limite:
Animals
Idioma:
En
Revista:
Ann Thorac Surg
Ano de publicação:
1999
Tipo de documento:
Article