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Xenotransplantation: Hyperacute and Delayed Xenograft Rejection

  • Chapter
Cardiac Allograft Rejection

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Abstract

According to the United Network for Organ Sharing (UNOS), patients waiting for a heart transplant in the U.S. have over a 20% mortality rate due to the shortage of donor organs.1 The scarcity of donor organs accounts, in part, for the strong resurgence of interest in xenotransplantation over the past decade. Although an unlimited availability of animal organs would rectify the existing crisis, there are formidable immunobiological barriers to overcome before the full potential of trans-species organ transplantation can be realized. The earliest and perhaps most devastating immunological barrier is that of hyperacute rejection, which results from the binding of natural antibody to the vascular endothelium, fixation of complement, activation of the endothelium, and finally, to the initiation of the coagulation cascade. Attempts to prevent this powerful immune response have targeted preformed natural antibodies and the complement system for intervention. The next immunological barrier, referred to as delayed xenograft rejection or acute vascular rejection, is less well understood but probably involves multiple pathways, including antibodies and/or immune cells binding to endothelium and endothelial cell activation (Figure 1). Of the last two immunological barriers, cellular rejection and chronic rejection, the former is probably best understood as it involves mechanisms which are similar in nature, albeit stronger in intensity, to those responsible for clinical allograft rejection. In contrast, the mechanisms responsible for chronic rejection remain enigmatic both in allogeneic and xenogeneic transplantation.

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References

  1. Reported deaths on the OPTN waiting List from 1988 through 1996. United Network for Organ Sharing. 1997.

    Google Scholar 

  2. Reemtsma K, McCracken BH, Schlegel JV, Pearl M. Heterotransplantation of the kidney: two clinical experiences. Science 1964;143:700.

    Article  PubMed  CAS  Google Scholar 

  3. Hardy JD, Chavez CM, Kurrus FD, et al. Heart transplantation in man. JAMA 1964;188:1132.

    Article  PubMed  CAS  Google Scholar 

  4. Beecher H, Adams RD, Barger AC, et al. A definition of reversible coma. JAMA 1968;205:85.

    Article  Google Scholar 

  5. Bailey LL, Nehlsen-Cannarella WSL, Concepcion W, Jolley WB. Baboon-to-human cardiac xenotransplantation in a neonate. JAMA 1985;254:3321.

    Article  PubMed  CAS  Google Scholar 

  6. Makowka L, Cramer DV, Hoffman A, et al. The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure. Transplantation 1995;59:1654.

    Article  Google Scholar 

  7. Groth CG, Korsgren O, Wennberg L, et al. Xenoislet rejection following pig-to-rat, pig-to-primate, and pig-to-man transplantation. Transplant Proc 1996;28:538.

    PubMed  CAS  Google Scholar 

  8. Ildstad ST. Xenotransplantation for AIDS. Lancet 1996;347:761.

    Article  PubMed  CAS  Google Scholar 

  9. Deacon T, Schumacher J, Dinsmore J, et al. Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson’s disease. Nature Medicine 1997;3:350.

    Article  PubMed  CAS  Google Scholar 

  10. Calne RY. Organ transplantation between widely disparate species. Transplant Proc 1970;2:550.

    PubMed  CAS  Google Scholar 

  11. Perper RJ, Najarian JS. Experimental renal heterotransplantation. I. In widely divergent species. Transplantation 1966;4:377.

    Article  PubMed  Google Scholar 

  12. Good AH, Cooper DKC, Malcolm AJ, et al. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant Proc 1992;24:559.

    PubMed  CAS  Google Scholar 

  13. Cooper DKC, Good AH, Koren E, et al. Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transplant Immunology 1993;1:198.

    Article  PubMed  CAS  Google Scholar 

  14. Galili U, Macher BA, Buehler J, Shohet SB. Human natural anti-a-galactosyl IgG. II. The specific recognition of α(l-3) linked galactose residues. J Exp Med 1985;162:573.

    Article  PubMed  CAS  Google Scholar 

  15. Galili U, Rachmilewitz EA, Peleg A, Flechner I. A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med 1984;160:1519.

    Article  PubMed  CAS  Google Scholar 

  16. Galili U, Mandrell RE, Hamadeh RM, Shohet SB, Griffiss JM. The interaction between the human natural anti-agalactosyl IgG (anti-Gal) and bacteria of the human flora. Infectious Immunology 1988;57:1730.

    Google Scholar 

  17. Rother RP, Fodor WL, Springhorn JP, et al. A novel mechanism of retrovirus inactivation in human serum mediated by anti-alpha-galactosyl natural antibody. J Exp Med 1995;182:1345.

    Article  PubMed  CAS  Google Scholar 

  18. Parker W, Bruno D, Holzknecht ZE, Piatt JL. Characterization and affinity isolation of xenoreac-tive human natural antibodies. J Immunol 1994;153:3791.

    PubMed  CAS  Google Scholar 

  19. Sandrin MS, Vaughan HA, Dabkowski PL, McKenzie IF. Anti-pig IgM antibodies in human serum react predominantly with Gal(alpha l-3)Gal epitopes. Proc Natl Acad Sci U S A 1993;90:11391.

    Article  PubMed  CAS  Google Scholar 

  20. Galili U, Tibell A, Samuelsson B, Rydberg L, Groth CG. Increased anti-Gal activity in diabetic patients transplanted with porcine islet cells. Transplant Proc 1996;28:564.

    PubMed  CAS  Google Scholar 

  21. Michler RE, Shah AS, Itescu S, et al. The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates. Journal of Thoracic and Cardiovascular Surgery 1996;112:1002.

    Article  PubMed  CAS  Google Scholar 

  22. Bartholomew A, Latinne D, Sachs DH, et al. Utility of xenografts: Lack of correlation between PRA and natural antibodies to swine. Xenotransplantation 1997;4:34.

    Article  Google Scholar 

  23. Miyagawa S, Hirose H, Shirakura R, et al. The mechanism of discordant xenograft rejection. Transplantation 1988;46:825.

    Article  PubMed  CAS  Google Scholar 

  24. Gambiez L, Weill BJ, Chereau C, Calmus Y, Houssin D. The hyperacute rejection of guinea pig to rat heart xenografts is mediated by preformed IgM. Transplant Proc 1990;22:1058.

    Google Scholar 

  25. Johnston PS, Wang MW, Lim SML, Wright LJ, White DJG. Discordant xenograft rejection in an antibody-free model. Transplantation 1992;54:573.

    Article  PubMed  CAS  Google Scholar 

  26. Sablinski T, Latinne D, Gianello P, et al. Xenotransplantation of pig kidneys to nonhuman primates: I. Development of the model. Xenotransplantation 1995;2:264.

    Article  Google Scholar 

  27. Dalmasso AP, Vercelolotti GM, Fischel RJ, Bolman RM, Bach FH, Piatt JL. Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients. Am J Pathol 1992;140:1157.

    PubMed  CAS  Google Scholar 

  28. Müller-Eberhard HJ. Complement: chemistry and pathways. In: Inflammation. Basic Principles and Clinical Correlates, Gallin JI, Goldstein IM, Snyderman R, eds. New York, Raven Press, 1992; 33.

    Google Scholar 

  29. Frank MM. Complement system. In: Samter’s Immunological Diseases, Frank MM, Austen KF, Claman HN, Unanue ER, eds. Boston, Little, Brown and Co., 1995;331.

    Google Scholar 

  30. Abbas AK, Lichtman AH, Pober JS. The complement system. In: Cellular and Molecular Immunology, Abbas AK, Lichtman AH, Pober JS, eds. Philadelphia, W.B. Saunders Co., 1994;225.

    Google Scholar 

  31. Auchincloss H, Sachs DH. Xenogeneic Transplantation. Annu Rev Immunol 1998;16:433.

    Article  PubMed  CAS  Google Scholar 

  32. Dalmasso AP, Vercelolotti GM, Piatt JL, Bach FH. Inhibition of complement-mediated endothelial cell cytotoxicity by decay-accelerating factor: Potential for prevention of xenograft hyperacute rejection. Transplantation 1991;52:530.

    Article  PubMed  CAS  Google Scholar 

  33. Bach FH. Xenotransplantation: Problems and prospects. Annual Reviews of Medicine 1998;49:301.

    Article  CAS  Google Scholar 

  34. Saadi S, Platt JL. Transient peturbation of endothelial integrity induced by natural antibodies and complement. J Exp Med 1995;181:21.

    Article  PubMed  CAS  Google Scholar 

  35. Platt JL, Vercelolotti GM, Lindman BJ, Oegema TR, Jr., Bach FH, Dalmasso AP. Release of heparan sulphate from endothelial cells: Implications for pathogenesis of hyperacute rejection. J Exp Med 1990;171:1363.

    Article  PubMed  CAS  Google Scholar 

  36. Parker W, Saadi S, Lin SS, Holzknecht ZE, Bustos M, Piatt JL. Transplantation of discordant xenografts: a challenge revisited. Immunology Today 1996;17:373.

    Article  PubMed  CAS  Google Scholar 

  37. Alexandre GPJ, Gianello P, Latinne D, et al. Plasmapheresis and splenectomy in experimental renal xenotransplantation. In: Xenograft 25, Hardy MA, ed. New York, Excerpta Medica, 1989;259.

    Google Scholar 

  38. Rydberg L, Hallberg E, Samuelsson B, et al. Studies on the removal of anti-pig xenoantibodies in the human by plasmapheresis/immunoadsorption. Xenotransplantation 1995;2:253.

    Article  Google Scholar 

  39. Gannedahl G, TufVeson G, Sundberg B, Groth CG. The effect of plasmapheresis and deoxysper-gualin or cyclophosphamide treatment on an anti-porcine Gal-a(l-3)-Gal antibody levels in humans. Xenotransplantation 1996;3:166.

    Article  Google Scholar 

  40. Cooper DKC, Human PA, Lexer G, et al. Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. Journal of Heart Transplantation 1988;7:238.

    PubMed  CAS  Google Scholar 

  41. Taniguchi S, Neethling FA, Korchagina EY, et al. In vivo immunoadsorption of anti-pig antibodies in baboons using a specific Galocl-3Gal column. Transplantation 1996;62:1379.

    Article  PubMed  CAS  Google Scholar 

  42. Kooyman DL, McClellan SB, Parker W, et al. Identification and characterization of a galactosyl peptide mimetic. Implications for use in removing xenoreactive anti-α Gal antibodies. Transplan¬tation 1996;61:851.

    Article  CAS  Google Scholar 

  43. Platt JL. Therapeutic strategies for hyperacute xenograft rejection. In: Hyperacute Xenograft Rejection, Piatt JL, ed. Austin, R.J. Landes Co., 1995;161.

    Google Scholar 

  44. Cooper DKC, Cairns TDH, Taube DH. Extracorporeal immunoadsorption of anti-pig antibody in baboons using cxGal oligosaccharide immunoaffinity columns. Xeno 1996;4:27.

    Google Scholar 

  45. Alexandre GPJ, Squifflet JP. Significance of the ABO antigen system. In: Organ Transplantation and Replacement, Cerilli GJ, ed. Philadelphia, J.B. Lippincott, 1988;223.

    Google Scholar 

  46. Alexandre GPJ, Squifflet JP, deBruyere M, et al. Present experiences in a series of 26 ABO-incom-patible living donor renal allografts. Transplant Proc 1987;19:4538.

    PubMed  CAS  Google Scholar 

  47. Piatt JL, Vercelolotti GM, Dalmasso AP, et al. Transplantation of discordant xenografts: A review of progress. Immunology Today 1990;11:450.

    Article  Google Scholar 

  48. Bach FH, Turman MA, Vercelolotti GM, Piatt JL, Dalmasso AP. Accommodation: a working paradigm for progressing toward clinical discordant xenografting. Transplant Proc 1991;23:205.

    PubMed  CAS  Google Scholar 

  49. Simon PM, Neethling FA, Taniguchi S, et al. Intravenous infusion of Galal-3Gal oligosaccharides in baboons delays hyperacute rejection of porcine heart xenografts. Transplantation 1998;65:346.

    Article  PubMed  CAS  Google Scholar 

  50. Koren E, Milotec F, Neethling FA, et al. Murine monoclonal anti-idiotypic antibodies directed against human anti-αGal antibodies prevent rejection of pig cells in culture: implications for pig-to-human organ xenotransplantation. Transplant Proc 1996;28:559.

    PubMed  CAS  Google Scholar 

  51. Koren E, Milotec F, Neethling FA, et al. Monoclonal anti-idiotypic antibodies neutralizes cytotoxic effects of anti-αGal antibodies. Transplantation 1996;62:837.

    Article  PubMed  CAS  Google Scholar 

  52. Yang YG, deGoma E, Ohdan H, et al. Tolerization of anti-Galalphal-3Gal natural antibody-forming B cells by induction of mixed chimerism. J Exp Med 1998;187:1335.

    Article  PubMed  CAS  Google Scholar 

  53. Leventhal JR, Dalmasso AP, Cromwell JW, et al. Prolongation of cardiac xenograft survival by depletion of complement. Transplantation 1993;55:857.

    Article  PubMed  CAS  Google Scholar 

  54. Candinas D, Lesnikoski BA, Robson SC, et al. Effect of repetitive high-dose treatment with soluble complement receptor type 1 and cobra venom factor on discordant xenograft survival. Transplantation 1996;62:336.

    Article  PubMed  CAS  Google Scholar 

  55. Kobayashi T, Taniguchi S, Ye Y, et al. Delayed xenograft rejection in C3-depleted discordant (pig-to-baboon) cardiac xenografts treated with cobra venom factor. Transplant Proc 1996;28:560.

    PubMed  CAS  Google Scholar 

  56. Pruitt SK, Baldwin WD, Marsh Jr HC, Linn SS, Yeh CG, Bollinger RR. The effect of soluble complement receptor type 1 on hyperacute xenograft rejection. Transplantation 1991;52:868.

    Article  PubMed  CAS  Google Scholar 

  57. Pruitt SK, Kirk AD, Bollinger RR, et al. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation 1994;57:363.

    Article  PubMed  CAS  Google Scholar 

  58. Weisman HF, Bartow T, Leppo MK, et al. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 1990;249:146

    Article  PubMed  Google Scholar 

  59. Cozzi E, White DJG. The generation of transgenic pigs as potential organs donors for humans. Nature Medicine 1995;1:964.

    Article  PubMed  CAS  Google Scholar 

  60. McCurry KR, Kooyman DL, Alvarado CG, et al. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. Nature Medicine 1995;1:423.

    Article  PubMed  CAS  Google Scholar 

  61. Medof ME, Kinoshita T, Nussenzweig V Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes. J Exp Med 1984;160:1558.

    Article  PubMed  CAS  Google Scholar 

  62. Rosengard AM, Cary NRB, Langford GA, Tucker AW, Wallwork J, White DJG. Tissue expression of human complement inhibitor, decay-accelerating factor, in transgenic pigs. Transplantation 1995;59:1325.

    PubMed  CAS  Google Scholar 

  63. Cozzi E, Tucker AW, Langford GA, et al. Characterization of pigs transgenic for human decay-accelerating factor. Transplantation 1997;64:1383.

    Article  PubMed  CAS  Google Scholar 

  64. Schmoeckel M, Nollert G, Shahmohammadi M, et al. Prevention of hyperacute rejection by human decay accelerating factor in xenogeneic perfused working hearts. Transplantation 1996;62:729.

    Article  PubMed  CAS  Google Scholar 

  65. Cozzi E, Yannoutsos N, Langford GA, Pinto-Chavez G, Wallwork J, White DJG. Effect of transgenic expression of human decay-accelerating factor on the inhibition of hyperacute rejection of pig organs. In: Xenotransplantation, Cooper DKC, Kemp E, Piatt JL, White DJG, eds. Heidelberg, Springer-Verlag, 1997;665.

    Chapter  Google Scholar 

  66. Schmoeckel M, Bhatti FNK, Zaidi A, et al. Orthotopic heart transplantation in a transgenic pig-to-primate model. Transplantation 1998;65:1570.

    Article  PubMed  CAS  Google Scholar 

  67. Diamond LE, McCurry KR, Martin MJ, et al. Characterization of transgenic pigs expressing functionally active human CD59 on cardiac endothelium. Transplantation 1996;61:1241.

    Article  PubMed  CAS  Google Scholar 

  68. Squinto SP. Genetically modified animal organs for human transplantation. World Journal of Surgery 1997;21:939.

    Article  PubMed  CAS  Google Scholar 

  69. Byrne GW, McCurry KR, Martin MJ, McClellan SM, Piatt JL, Logan JS. Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage. Transplantation 1997;63:149.

    Article  PubMed  Google Scholar 

  70. Sandrin MS, Fodor WL, Mouhtouris E, et al. Enzymatic remodeling of the carbohydrate surface of a xenogeneic cell substantially reduces human antibody binding and complement-mediated cytoly-sis. Nature Medicine 1995;1:1261–1267.

    Article  PubMed  CAS  Google Scholar 

  71. Sandrin MS, Fodor WL, Cohney S, et al. Reduction of the major porcine xenoantigen Gala (1,3)Gal by expression of a (1,2) fucosyltransferase. Xenotransplantation 1996;3:134.

    Article  Google Scholar 

  72. Chen C, Fisicaro N, Shinkel TA, et al. Reduction in Gal-α1,3-Gal epitope expression in transgenic mice expressing human H-transferase. Xenotransplantation 1996;3:69.

    Article  Google Scholar 

  73. Koike C, Kannagi R, Takuma Y, et al. Introduction of α (1,2)-fucosytransferase and its effect on αGal epitopes in transgenic pig. Xenotransplantation 1996;3:81.

    Article  Google Scholar 

  74. Cooper DKC, Koren E, Oriol R. Genetically-engineered pigs. Lancet 1993;342:682.

    Article  PubMed  CAS  Google Scholar 

  75. Thall AD, Murphy HS, Lowe JB. Α1,3-Galactosyltransferase-deficient mice produce naturally occurring cytotoxic anti-Gal antibodies. Transplant Proc 1996;28:556.

    PubMed  CAS  Google Scholar 

  76. Tearle RG, Tange MJ, Zanettino ZL, et al. The α1,3-galactosyltransferase knock-out mouse. Implications for xenotransplantation. Transplantation 1996;61:13.

    Article  PubMed  CAS  Google Scholar 

  77. McKenzie IF, Cohney S, Vaughan HA, et al. Overcoming the anti-αGal(1–3)Gal reaction in xenotransplantation. Xenotransplantation 1995;3:86.

    Google Scholar 

  78. Cooper DKC. Xenoantigens and xenoantibodies. Xenotransplantation 1998;5:6.

    Article  PubMed  CAS  Google Scholar 

  79. Hasan R, Van den Bogaerde JB, Wallwork J, White DJG. Evidence that long-term survival of concordant xenografts is achieved by inhibition of antispecies antibody production. Transplantation 1992;54:408.

    Article  PubMed  CAS  Google Scholar 

  80. Minanov OP, Itescu S, Neethling FA, et al. Anti-Gal IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation. Transplantation 1997;63:182.

    Article  PubMed  CAS  Google Scholar 

  81. Goodman DJ, Millan M, Ferran C, Bach FH. Mechanism of delayed xenograft rejection. In: Xenotransplantation: The transplantation of organs and tissues between species, Cooper DKC, Kemp E, Piatt JL, White DJG, eds. Heidelberg, Springer, 1997;77.

    Google Scholar 

  82. Blakely ML, Van der Werf WJ, Berndt MC, Dalmasso AP, Bach FH, Hancock WW. Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation 1994;58:1059.

    PubMed  CAS  Google Scholar 

  83. Robertson MJ, Ritz J. Role of IL-2 receptors in NK cell activation and proliferation. In: NK Cell-Mediated Cytotoxicity: Receptors, Signaling and Mechanism, Lotzova E, Herberman RB, eds. Boca Raton, CRC Press, 1992;183.

    Google Scholar 

  84. Robson SC, Siegel JB, Lesnikoski BA, et al. Aggregation of human platelets induced by porcine endothelial cells is dependent upon both activation of complement and thrombin generation. Xenotransplantation 1996;3:24.

    Article  Google Scholar 

  85. Robson SC, Kaczmarek E, Siegel JB, et al. Loss of ATP diphosphohydrolase activity with endothelial cell activation. J Exp Med 1997;185:153.

    Article  PubMed  CAS  Google Scholar 

  86. Bach FH. Genetic engineering as an approach to xenotransplantation. World Journal of Surgery 1997;21:913.

    Article  PubMed  CAS  Google Scholar 

  87. Esmon CT. Cell mediated events that control blood coagulation and vascular injury. Annual Review of Cell Biology 1993;9:1.

    Article  PubMed  CAS  Google Scholar 

  88. Balla G, Jacob HS, Balla J, et al. Ferritin: A cytoprotective antioxidant stratagem of endothelium. Journal of Biological Chemistry 1992;267:18148.

    PubMed  CAS  Google Scholar 

  89. Piatt JL, Dalmasso AP, Lindman BJ, Ihrcke NS, Bach FH. The role of C5a and antibody in the release of heparan sulfate from endothelial cells. Eur J Immunol 1991;21:2287.

    Google Scholar 

  90. Whelan J, Ghersa P, van Huijsduijnen RH, et al. An NFkB-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Research 1991;19:2645.

    Article  PubMed  CAS  Google Scholar 

  91. deMartin R, Vanhove B, Cheng Q, et al. Cytokine-inducible expression in endothelial cells of an IkBα-like gene is regulated by NFkB. EMBO Journal 1993;12:2773.

    PubMed  Google Scholar 

  92. Cogswell JP, Godlevski MM, Wisely GB, et al. NF-kB regulates IL-1B transcription through a consensus NF-kB binding site and a nonconsensus CRE-like site. J Immunol 1994;153:712.

    PubMed  CAS  Google Scholar 

  93. Millan MT, Geczy C, Stuhlmeier KM, Goodman DJ, Ferran C, Bach FH. Human monocytes activate porcine endothelial cells, resulting in increased E-selectin, interleukin-8, monocyte chemotac-tic protein-1, and plasminogen activator inhibitor-type-1 expression. Transplantation 1997;63:421.

    Article  PubMed  CAS  Google Scholar 

  94. Waterworth PD, Cozzi E, Tolan MJ, Langford G, Braidley P, Chavez G, Dunning J, Wallwork J, White D. Pig-to-primate cardiac xenotransplantation and cyclophosphamide therapy Transplant Proc 1997;29:899-900.

    CAS  Google Scholar 

  95. Voraberger G, Schafer R, Stratowa C. Cloning of the human gene for intercellular adhesion molecule 1 and analysis of its 5’-regulatory region. J Immunol 1991;147:2777.

    PubMed  CAS  Google Scholar 

  96. Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-kB. Annual Review of Cell Biology 1994;10:405.

    Article  PubMed  CAS  Google Scholar 

  97. Finco TS, Baldwin AS, Jr. Mechanistic aspects of NF-kB regulation: The emerging role of phosphorylation and proteolysis. Immunity 1995;3:263.

    CAS  Google Scholar 

  98. DiDonato J, Mercurio F, Rosette C, et al. Mapping of the inducible IkB phosphorylation sites that signal its ubiquitination and degradation. Molecular and Cellular Biology 1996;16:1295.

    PubMed  CAS  Google Scholar 

  99. Beg AA, Finco TS, Nantermet PV, Baldwin AS, Jr. Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IkBα: a mechanism for NF-kB activation. Molecular and Cellular Biology 1993;13:3301.

    PubMed  CAS  Google Scholar 

  100. Henkle T, Machieldt T, Alkalay I, Kronke M, Ben-Nerial Y, Baeuerie PA. Rapid proteolysis of IkBcc is necessary for activation of transcription factor NF-kB. Nature 1993;365:182.

    Article  Google Scholar 

  101. Cooper JT, Stroka DM, Brostjian C, Palmetshofer A, Bach FH, Ferran C. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. Journal of Biological Chemistry 1996;271:18068.

    Article  PubMed  CAS  Google Scholar 

  102. Bach FH, Ferran C, Hechenleitner P, et al. Accommodation of vascularized xenografts: Expression of “protective genes” by donor endothelial cells in a host Th2 cytokine environment. Nature Medicine 1997;3:196.

    Article  PubMed  CAS  Google Scholar 

  103. Goodman DJ, von Albertini MA, McShea A, Wrighton CJ, Bach FH. Adenoviral-mediated overex-pression of IkBα in endothelial cells inhibits natural killer cell-mediated endothelial cell activation. Transplantation 1996;62:967.

    Article  PubMed  CAS  Google Scholar 

  104. Stroka DM, Copper ML, Brostjian C, et al. Expression of a negative dominant mutant of human P55 tumor necrosis factor-receptor inhibits TNF and monocyte-induced activation in porcine aortic endothelial cells. Transplant Proc 1997;29:882.

    Article  PubMed  CAS  Google Scholar 

  105. Ildstad ST, Bluestone JA, Barbieri S, Sachs DH. Characterization of mixed allogeneic chimeras. Immunocompetence, in vitro reactivity, and genetic specificity of tolerance. J Exp Med 1985;162:231.

    Article  PubMed  CAS  Google Scholar 

  106. Sykes M, Sachs DH. Mixed allogeneic chimerism as an approach to transplantation tolerance. Immunology Today 1988;9:23.

    Article  PubMed  CAS  Google Scholar 

  107. Sachs DH, Sykes M, Greenstein J, Cosimi AB. Tolerance and xenograft survival. Nature Medicine 1995;969.

    Google Scholar 

  108. Sablinski T, Gianello PR, Bailin M, et al. Pig to monkey bone marrow and kidney xenotransplantation. Surgery 1997;121:381.

    Article  PubMed  CAS  Google Scholar 

  109. Sharabi Y, Sachs DH. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. J Exp Med 1989;169:493.

    Article  PubMed  Google Scholar 

  110. Xu Y, Lorf T, Sablinski T, et al. Removal of anti-porcine natural antibodies from human and non-human primate plasma in vitro and in vivo by a Gakαl-3Galbl-4bGlc-X immunoaffinity column. Transplantation 1998;65:172.

    Article  PubMed  CAS  Google Scholar 

  111. Kozlowski T, Fuchimoto Y, Monroy R, et al. Apheresis and column absorption for specific removal of Gal-alpha-1,3 Gal natural antibodies in a pig-to-baboon model. Transplant Proc 1997;29:961.

    Article  PubMed  CAS  Google Scholar 

  112. Latinne D, Gianello P, Smith CV, et al. Xenotransplantation from pig to cynomolgus monkey: Approach toward tolerance induction. Transplant Proc 1993;25:336.

    PubMed  CAS  Google Scholar 

  113. Tanaka M, Latinne D, Gianello P, et al. Xenotransplantation from pig to cynomolgus monkey: The potential for overcoming xenograft rejection through induction of chimerism. Transplant Proc 1994;26:1326.

    PubMed  CAS  Google Scholar 

  114. Sachs DH, Sablinski T. Tolerance across discordant xenogeneic barriers. Xeno 1995;2:234.

    Article  Google Scholar 

  115. Madsen JC, Yamada K, Allan JS, et al. Prevention of cardiac allograft vasculopathy across class I MHC disparities by the induction of transplantation tolerance. Transplantation 1998;65:304.

    Article  PubMed  CAS  Google Scholar 

  116. Piatt JL. The immunological barriers to xenotransplantation. Critical Reviews in Immunology 1996;16:331.

    Google Scholar 

  117. Cooper DKC, Kemp E, Reemstsma K, White DJG, eds. Xeno-transplantation—The Transplantation of Organs Between Species. Berlin: Springer, 1997.

    Google Scholar 

  118. Atkinson JP, Oglesby TJ, White D, Adams EA, Liszewski MK. Separation of self from non-self in the complement system: a role for membrane cofactor protein and decay accelerating factor. Clin Exp Immunol 1991;86:27.

    Google Scholar 

  119. Lambrigts D, Sachs DH, Cooper DKC, Discordant organ xenotransplantation in primates: world experience and current status. Transplantation 1998;66:547.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiac Surgery and Transplantation Biology Research Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Kwabena Mawulawde M.D. & Joren C. Madsen M.D., D.Phil

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  1. Kwabena Mawulawde M.D.
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  2. Joren C. Madsen M.D., D.Phil
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Editors and Affiliations

  1. Heart Failure & Transplantation Service, Harvard Medical School, Bigelow 645, 55 Fruit Street, Boston, Massachusetts, 02114, USA

    G William Dec M.D.

  2. Heart Failure/Transplantation Center, Hahnemann University School of Medicine, Broad and Vine Streets, Mail Stop 115, Philadelphia, Pennsylvania, 19102, USA

    Jagat Narula M.D., Ph.D. (Director) (Director)

  3. Department of Cardiology, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Roure 80, 25198, Lleida, Spain

    Manel Ballester M.D. (Chairman) (Chairman)

  4. Nuclear Medicine Department, Hospital de Sant Pau, Autonomous University of Barcelona, Pare Claret 167, 08025, Barcelona, Spain

    Ignasi Carrio M.D. (Director) (Director)

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© 2001 Springer Science+Business Media New York

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Mawulawde, K., Madsen, J.C. (2001). Xenotransplantation: Hyperacute and Delayed Xenograft Rejection. In: Dec, G.W., Narula, J., Ballester, M., Carrio, I. (eds) Cardiac Allograft Rejection. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1649-1_8

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  • DOI: https://doi.org/10.1007/978-1-4615-1649-1_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5659-2

  • Online ISBN: 978-1-4615-1649-1

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