April 1, 1996Open Access
View Full PaperDifferential localization of allograft nitric oxide synthesis: comparison of liver and heart transplantation in the rat model
Key Result
Acute rejection in rat heart and liver allografts was associated with elevated systemic nitrite and increased graft iNOS protein, with differential cellular expression of iNOS mRNA between organs.
Structured PICO
P
Population
Rat models of heterotopic heart and orthotopic liver transplantation used to study acute rejection.
E
Exposure
Heterotopic heart and orthotopic liver allografts (acute rejection model)
C
Comparator
Naive controls and isografted animals
O
Outcome
Systemic levels of nitrite, graft iNOS protein content, and cellular localization of iNOS mRNAsurrogate
Organ-specific differential cellular expression of iNOS occurs during acute allograft rejection, with cardiac myocytes not expressing iNOS mRNA unlike hepatocytes.
Abstract
Nitric oxide (NO) is a free radical with a diversity of cellular origins and potential functions. Within the realm of solid organ transplantation, NO has been the focus of much attention. Discordant reports have documented both suppression and potentiation of the alloimmune response. In addition to questions regarding its functional role, little is known of the cellular origins of NO in acute rejection of vascularized allografts. To address this question, acute rejection models of rat heterotopic heart and orthotopic liver transplantation were chosen. When compared with naive controls and isografted animals, acute rejection in both heart and liver transplantation was associated with elevated systemic levels of the NO metabolite, nitrite. This was accompanied by increased graft content of iNOS protein as determined by immunoblot analysis of protein extracts. Expression of iNOS mRNA was localized with in situ hybridization. In both heart and liver transplantation, iNOS mRNA was found in the inflammatory infiltrate accompanying acute rejection. In addition, hepatocytes also expressed iNOS mRNA in the rejecting liver allograft. In contrast, cardiac myocytes in the rejecting heart allograft did not stain for iNOS mRNA. These results indicate that organ-specific, differential cellular expression of iNOS occurs in the acutely rejecting allograft. Transcriptional regulation of iNOS may vary among various organs according to the local cellular milieu. In addition, there may be a variable allograft specific response to acute rejection which may modify the associated immunologic biology.