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Modification of vascular responses in xenotransplantation: Inflammation and apoptosis

Nature Medicine volume 3, pages 944–948 (1997)Cite this article

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References

  1. Blakely, M.L., van der Werf, W.J., Dalmasso, A.P., Bach, F. H. & Hancock, W.W. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation 58, 1059–1066 (1994).

    Article  CAS  Google Scholar 

  2. Bach, F.H., Winkler, H., Ferran, C., Hancock, W.W. & Robson, S.C. Delayed xenograft rejection. Immunol. Today 17, 379–384 (1996).

    Article  CAS  Google Scholar 

  3. Candinas, D., Koyamada, N., Miyatake, T., Bach, F.H. & Hancock, W.W. T cell-independence of macrophage and NK cell infiltration, cytokine production and endothelial activation during delayed xenograft rejection. Transplantation 62, 1920–1926 (1996).

    Article  CAS  Google Scholar 

  4. Dalmasso, A.P., Varcellotti, C.M., Platt, J.L. & Bach, F.H. Inhibition of complement-mediated endothelial cell cytotoxicity by decay-accelerating factor. Potential for prevention of xenograft hyperacute rejection. Transplantation. 52, 530–534 (1991).

    Article  CAS  Google Scholar 

  5. Bach, F.H., Turman, M.A., Varcellotti, C. M., Platt, J.L. & Dalmasso, A.P. Accommodation: a working paradigm for progressing toward clinical discordant xenografting. Transplant. Proc. 23, 205–207 (1991).

    CAS  PubMed  Google Scholar 

  6. Dalamsso, A.P. & Bach, F.H. Expression of human regulators of complement on pig endothelial cells. Xenotransplantation 4, 55–57 (1996).

    Google Scholar 

  7. Pruit, S.K. et al. Effect of continuous complement inhibition using soluble complement receptor type 1 on survival of pig-to-primate cardiac xenografts. Transplantation 63, 900–905 (1997).

    Article  Google Scholar 

  8. Bach, F.H. et al. Accomodation of vascularized xenografts: expression of “protective genes” by donor endothelial cells in a host Th2 cytokine environment. Nature Med. 3, 196–204 (1997).

    Article  CAS  Google Scholar 

  9. Hechenleitner, P. et al. Protective genes expressed in endothelial cells of second hamster heart transplants to rats carrying an accommodated first graft. Xenotransplantation 3, 279–286 (1996).

    Article  Google Scholar 

  10. Mark, W. et al. Xenograft accommodation is accomplished by intragraft Th2 cytokines and expression of protective genes. Xenotransplantation (in the press).

  11. Cowan, P.J. et al. Targeting gene expression of endothelial cells in transgenic mice using the human intercellular adhesion molecule 2 promoter. Transplantation 62, 155–160 (1996).

    Article  CAS  Google Scholar 

  12. Tran, T.H. Anrather, J., Hancock, W. W., Bach, F.H. & Winkler, H. Tetracycline regulated endothelial cell specific expression of a transdominant inhibitor of NF-kB in trans-genie mice. Transplant. Proc. (in the press).

  13. Krikos, A., Laherty, C.D. & Dixit, V.M. Transcriptional activation of theTNFa-inducible zinc finger protein, A20, is mediated by kB elements. J. Biol. Chem. 267, 17971–17976 (1992).

    CAS  PubMed  Google Scholar 

  14. Cooper, J.T. et al. A20 blocks endothelial cell activation through a NF-kB-dependent mechanism. J. Biol. Chem. 271, 18068–18073 (1996).

    Article  CAS  Google Scholar 

  15. Ferran, C. & Stroka, D. Adenovirus-mediated gene transfer of A20 renders endothelial cells resistant to activation: a means of evaluating the role of EC activation in xenograft rejection. Transplant. Proc. 29, 879–880 (1997).

    Article  CAS  Google Scholar 

  16. Bach, F.H., Hancock, W.W. & Ferran, C. Protective genes expressed in endothelial cells: A regulatory response to injury. Immunol. Today (in the press)

  17. Sandrin et al. Enzymatic remodelling of the carbohydrate surface of a xenogeneic cell substantially reduces human antibody binding and complement-mediated lysis. Nature Med. 1, 1261–1267 (1995).

    Article  CAS  Google Scholar 

  18. Robson, S.C. et al. Thrombin inhibition in an ex vivo model of porcine heart xenograft hyperacute rejection. Transplantation 61, 862–868 (1996).

    Article  CAS  Google Scholar 

  19. Lesnikoski, B.A., Candinas, D., Siegel, J.B., Bach, F.H. & Robson, S.C. Antithrombin agents in xenograft rejection. Xenotransplantation (in the press).

  20. Goodman, D.J., von Albertini, M., Willson, A., Millan, M.T. & Bach, F.H. Direct activation of porcine endothelial cells by human natural killer cells. Transplantation 61, 763–771 (1996).

    Article  CAS  Google Scholar 

  21. Millan, M.T. et al. Human monocytes activate porcine endothelial cells, resulting in increased E-selectin, interleukin-8, monocyte chemotactic protein-1, and plasmino-gen activator inhibitor type-1 expression. Transplantation 63, 421–429 (1997).

    Article  CAS  Google Scholar 

  22. Inverardi, L. et al. Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 63, 1318–1330 (1997).

    Article  CAS  Google Scholar 

  23. Hancock, W.W. et al. Effects of leflunomide and deoxyspergualin in the guinea pig->rat cardiac model of delayed xenograft rejection: Suppression of B cell and C-C chemokine responses but not induction of macrophage lectin. Transplantation (in the press).

  24. Kopp, C.W. et al. Effect of porcine endothelial tissue factor pathway inhibitor on human coagulation factors. Transplantation 63, 749–758 (1997).

    Article  CAS  Google Scholar 

  25. Siegel, J. et al. Activation of human prothrombin by porcine endothelium. Transplantation (in the press).

  26. Lawson, J.H. & Platt, J.L. Molecular barriers to xenotransplantation. Transplantation 62, 303–310 (1996).

    Article  CAS  Google Scholar 

  27. Esmon, C.T. & Fukudome, K. Cellular regulation of the protein C pathway. Semin. Cell Biol. 6, 259–68 (1995).

    Article  CAS  Google Scholar 

  28. Grey, S.T. & Hancock, W.W. A physiologic anti-inflammatory pathway based upon thrombomodulin expression and generation of activated protein C by human mononuclear phagocytes. J. Immunol. 156, 2256–2263 (1996).

    CAS  PubMed  Google Scholar 

  29. Hancock, W. & Bach, F. H. Immunobiology and therapeutic applications of protein C/protein S/ thrombomodulin in human and experimental allo-and xenotransplantation. Trends Cardiovasc. Med. (in the press).

  30. Wrighton, C., Kopp, C.W., McShea, A., Vetr, H. & Bach, F.H. High level of functional human thrombomodulin in cultured porcine aortic endothelial cells. Transplant. Proc. 27, 288–289 (1995).

    CAS  PubMed  Google Scholar 

  31. Coughlan, A.F., Berndt, M.C., Dunlop, L.C. & Hancock, W.W. In vivo studies of P-selectin and platelet-activating factor during endotoxemia, accelerated allograft rejection, and discordant xenograft rejection. Transplant. Proc. 25, 2930–2931 (1993).

    CAS  PubMed  Google Scholar 

  32. Kaczmarek, E. et al. Identification and characterization of CD39 as the vascular ATPDase. In: Ecto-ATPases. Proc. First Int. Workshop on Ecto-ATPases. Editors: L. Plesner, Kirley TL and Knowles AF. Plenum. New York. 1997. pp. 171–185.

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Author notes

  1. Fritz H. Bach, Christiane Ferran & Miguel Soares

    Present address: Sandoz Center for Immunobiology and Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA

  2. Christopher J. Wrighton

    Present address: Therexsys, The Science Park, University of Keele, Keele, Staffordshire, STS SSP, UK

Authors and Affiliations

  1. Sandoz Center for Immunobiology and Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, 02215, USA

    Christopher J. Wrighton, Josef Anrather, Hans Winkler, Simon C. Robson & Wayne W. Hancock

  2. Therexsys, The Science Park, University of Keele, Keele, Staffordshire, STS SSP, UK

    Josef Anrather, Hans Winkler, Simon C. Robson & Wayne W. Hancock

Authors
  1. Fritz H. Bach
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  2. Christiane Ferran
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  4. Christopher J. Wrighton
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  5. Josef Anrather
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  6. Hans Winkler
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  7. Simon C. Robson
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  8. Wayne W. Hancock
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Bach, F., Ferran, C., Soares, M. et al. Modification of vascular responses in xenotransplantation: Inflammation and apoptosis. Nat Med 3, 944–948 (1997). https://doi.org/10.1038/nm0997-944

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