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. 1996 Apr;87(4):647–653. doi: 10.1046/j.1365-2567.1996.468592.x

Differential localization of allograft nitric oxide synthesis: comparison of liver and heart transplantation in the rat model.

P C Kuo 1, E J Alfrey 1, N R Krieger 1, K Y Abe 1, P Huie 1, R K Sibley 1, D C Dafoe 1
PMCID: PMC1384146  PMID: 8675222

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.

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Selected References

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  1. Bastian N. R., Xu S., Shao X. L., Shelby J., Granger D. L., Hibbs J. B., Jr N omega -monomethyl-L-arginine inhibits nitric oxide production in murine cardiac allografts but does not affect graft rejection. Biochim Biophys Acta. 1994 May 25;1226(2):225–231. doi: 10.1016/0925-4439(94)90033-7. [DOI] [PubMed] [Google Scholar]
  2. Cattell V., Smith J., Jansen A., Riveros-Moreno V., Moncada S. Localization of inducible nitric oxide synthase in acute renal allograft rejection in the rat. Transplantation. 1994 Dec 27;58(12):1399–1402. [PubMed] [Google Scholar]
  3. Devlin J., Palmer R. M., Gonde C. E., O'Grady J., Heaton N., Tan K. C., Martin J. F., Moncada S., Williams R. Nitric oxide generation. A predictive parameter of acute allograft rejection. Transplantation. 1994 Sep 15;58(5):592–595. [PubMed] [Google Scholar]
  4. Gaboury J., Woodman R. C., Granger D. N., Reinhardt P., Kubes P. Nitric oxide prevents leukocyte adherence: role of superoxide. Am J Physiol. 1993 Sep;265(3 Pt 2):H862–H867. doi: 10.1152/ajpheart.1993.265.3.H862. [DOI] [PubMed] [Google Scholar]
  5. Gregory C. R., Huie P., Billingham M. E., Morris R. E. Rapamycin inhibits arterial intimal thickening caused by both alloimmune and mechanical injury. Its effect on cellular, growth factor, and cytokine response in injured vessels. Transplantation. 1993 Jun;55(6):1409–1418. doi: 10.1097/00007890-199306000-00037. [DOI] [PubMed] [Google Scholar]
  6. Gregory S. H., Sagnimeni A. J., Wing E. J. Arginine analogues suppress antigen-specific and -nonspecific T lymphocyte proliferation. Cell Immunol. 1994 Feb;153(2):527–532. doi: 10.1006/cimm.1994.1048. [DOI] [PubMed] [Google Scholar]
  7. Huot A. E., Moore A. L., Roberts J. D., Hacker M. P. Nitric oxide modulates lymphocyte proliferation but not secretion of IL-2. Immunol Invest. 1993 Jun;22(4):319–327. doi: 10.3109/08820139309063411. [DOI] [PubMed] [Google Scholar]
  8. Kamada N., Calne R. Y. A surgical experience with five hundred thirty liver transplants in the rat. Surgery. 1983 Jan;93(1 Pt 1):64–69. [PubMed] [Google Scholar]
  9. Kubes P., Kanwar S., Niu X. F., Gaboury J. P. Nitric oxide synthesis inhibition induces leukocyte adhesion via superoxide and mast cells. FASEB J. 1993 Oct;7(13):1293–1299. doi: 10.1096/fasebj.7.13.8405815. [DOI] [PubMed] [Google Scholar]
  10. Kubes P., Suzuki M., Granger D. N. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4651–4655. doi: 10.1073/pnas.88.11.4651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuo P. C., Abe K. Y. Interleukin 1-induced production of nitric oxide inhibits benzenetriol-mediated oxidative injury in rat hepatocytes. Gastroenterology. 1995 Jul;109(1):206–216. doi: 10.1016/0016-5085(95)90286-4. [DOI] [PubMed] [Google Scholar]
  12. Kuo P. C., Alfrey E. J., Abe K. Y., Huie P., Sibley R. K., Dafoe D. C. Cellular localization and effect of nitric oxide synthesis in a rat model of orthotopic liver transplantation. Transplantation. 1996 Jan 27;61(2):305–312. doi: 10.1097/00007890-199601270-00024. [DOI] [PubMed] [Google Scholar]
  13. Kuo P. C., Slivka A. Nitric oxide decreases oxidant-mediated hepatocyte injury. J Surg Res. 1994 Jun;56(6):594–600. doi: 10.1006/jsre.1994.1094. [DOI] [PubMed] [Google Scholar]
  14. Langrehr J. M., Hoffman R. A., Billiar T. R., Lee K. K., Schraut W. H., Simmons R. L. Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism. Surgery. 1991 Aug;110(2):335–342. [PubMed] [Google Scholar]
  15. Langrehr J. M., Murase N., Markus P. M., Cai X., Neuhaus P., Schraut W., Simmons R. L., Hoffman R. A. Nitric oxide production in host-versus-graft and graft-versus-host reactions in the rat. J Clin Invest. 1992 Aug;90(2):679–683. doi: 10.1172/JCI115911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lipton S. A., Choi Y. B., Pan Z. H., Lei S. Z., Chen H. S., Sucher N. J., Loscalzo J., Singel D. J., Stamler J. S. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 1993 Aug 12;364(6438):626–632. doi: 10.1038/364626a0. [DOI] [PubMed] [Google Scholar]
  17. Lyons C. R., Orloff G. J., Cunningham J. M. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem. 1992 Mar 25;267(9):6370–6374. [PubMed] [Google Scholar]
  18. Morris S. M., Jr, Billiar T. R. New insights into the regulation of inducible nitric oxide synthesis. Am J Physiol. 1994 Jun;266(6 Pt 1):E829–E839. doi: 10.1152/ajpendo.1994.266.6.E829. [DOI] [PubMed] [Google Scholar]
  19. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  20. Ono K., Lindsey E. S. Improved technique of heart transplantation in rats. J Thorac Cardiovasc Surg. 1969 Feb;57(2):225–229. [PubMed] [Google Scholar]
  21. Roland C. R., Walp L., Stack R. M., Flye M. W. Outcome of Kupffer cell antigen presentation to a cloned murine Th1 lymphocyte depends on the inducibility of nitric oxide synthase by IFN-gamma. J Immunol. 1994 Dec 15;153(12):5453–5464. [PubMed] [Google Scholar]
  22. Rubbo H., Radi R., Trujillo M., Telleri R., Kalyanaraman B., Barnes S., Kirk M., Freeman B. A. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem. 1994 Oct 21;269(42):26066–26075. [PubMed] [Google Scholar]
  23. Worrall N. K., Lazenby W. D., Misko T. P., Lin T. S., Rodi C. P., Manning P. T., Tilton R. G., Williamson J. R., Ferguson T. B., Jr Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase. J Exp Med. 1995 Jan 1;181(1):63–70. doi: 10.1084/jem.181.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yang X., Chowdhury N., Cai B., Brett J., Marboe C., Sciacca R. R., Michler R. E., Cannon P. J. Induction of myocardial nitric oxide synthase by cardiac allograft rejection. J Clin Invest. 1994 Aug;94(2):714–721. doi: 10.1172/JCI117390. [DOI] [PMC free article] [PubMed] [Google Scholar]

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