Advertisement

Anti-Gal, α-Gal Epitopes, and Xenotransplantation

  • Takaaki Kobayashi
  • David K. C. Cooper
Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 32)

Abstract

Significant progress in clinical transplantation has been achieved through the development of improved immunosuppressive therapy during the past two decades. Transplantation is clearly established as the treatment of choice for many patients suffering from end-stage organ failure. Although the number of organ donors becoming available has slowly increased, the relative shortage of organ donors caused by the extended indications for transplantation has become critical. Attention is now being focused on xenotransplantation—using animal organs, tissues or cells—as a potential and promising solution to this serious problem (Cooper, 1993a).

Keywords

Natural Antibody Hyperacute Rejection Xenograft Rejection Antiidiotypic Antibody Porcine Endothelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alexandre, G. P., Squifflet. J. P., De. B. M., Latinne. D., Reding. R., Gianello. P., Carlier. M., and Pirson, Y., 1987. Present experiences in a series of 26 ABO-incompatible living donor renal allografts. Transplant. Proc. 19: 4538–42.PubMedGoogle Scholar
  2. Alexandre, G. P. J., Gianello, P., Latinne, D., Carlier, M., Dewaele, C. A., Van Obbergh, L., Moriau, M., Marbaix, E., Lambotte, J. L., and Squifflet, L. P., 1989, Plasmapheresis and splenectomy in experimental renal xenotransplantation. In: Xenograft 25, (MA. Hardy, ed), Elsevier, New York, pp. 259–266.Google Scholar
  3. Alvarado, C. G., Cotterell, A. H., McCurry, K. R., Collins, B. H., Magee, J. C., Berthold, J., Logan, J. S., and Platt, J. L., 1995, Variation in the level of xenoantigen expression in porcine organs. Transplantation. 59: 1589–96.PubMedGoogle Scholar
  4. Aspeslet, L. J., Chackowsky, P., Sekhon, H., Malcolm, A. J., Mosleh, Z., Koshal, A., and Yatscoff, R. W., 1996, Identification of porcine membrane antigens involved in the cytotoxic response mediated by human xenoreactive antibodies. Xenotransplantation. 3: 1–10.Google Scholar
  5. Auchincloss, H. J., 1988, Xenogeneic transplantation. A review. Transplantation. 46: 1–20PubMedGoogle Scholar
  6. Bach, F. H., Turman, M. A., Vercellotti, G. M., Platt. J. L., and Dalmasso, A. P., 1991, Accommodation: a working paradigm for progressing toward clinical discordant xenografting. Transplant. Proc. 23: 205–7.PubMedGoogle Scholar
  7. Bach, F. H., Winkler, H., Ferran, C., Hancock, W. W., and Robson, S. C., 1996, Delayed xenograft rejection. Immunol. Today. 17: 379–84.PubMedGoogle Scholar
  8. Bach, F. H., Ferran, C., Soares, M., Wrighton, C. J., Anrather, J., Winkler, H., Robson, S. C., and Hancock, W. W., 1997, Modification of vascular responses in xenotransplantation: inflammation and apoptosis. Nature Med. 3: 944–948.PubMedGoogle Scholar
  9. Bannett, A. D., McAlack, R. F., Raja, R., Baquero, A., and Morris, M., 1987, Experiences with known ABO-mismatched renal transplants. Transplant. Proc. 19: 4543–6.PubMedGoogle Scholar
  10. Blakely, M. L., Van der, Werf, Wj, Berndt, M. C., Dalmasso, A. P., Bach, F. H., and Hancock, W. W., 1994, Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection. Transplantation. 58: 1059–66.PubMedGoogle Scholar
  11. Borche, L., Thibaudeau, K., Navenot, J. M., Soulillou, J. P., and Blanchard, D., 1994, Cytolytic effect of human anti-Gal IgM and complement on porcine endothelial cells: a kinetic analysis. Xenotransplantation. 1: 125–131.Google Scholar
  12. Bouhours, D. and Bouhours, J.-F., 1994, Hanganutziu-Deicher xenoantigens. Xeno. 2: 33–34.Google Scholar
  13. Bouhours, D., Liaigre, J., Naulet, J., Maume, D., and Bouhours, J. F., 1997, A novel glycosphingolipid expressed in pig kidney: Galα1–3Lewis(x) hexaglycosylceramide. Glycoconjugate J. 14: 29–38.Google Scholar
  14. Brauer, R. B., Baldwin, W. D., Daha, M. R., Pruitt, S. K., and Sanfilippo, F., 1993, Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of discordant cardiac xenografts. J. Immunol. 151: 7240–8.PubMedGoogle Scholar
  15. Bruggemann, M., Williams, G. T., Bindon, C. I., Clark, M. R., Walker, M. R., Jefferis, R., Waldmann, H., and Neuberger, M. S., 1987, Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies. J. Exp. Med. 166: 1351–61.PubMedGoogle Scholar
  16. Cairns, T., Hammelmann, W., Gray, D., Welsh, K., and Larson, G., 1994, Enzymatic removal from various tissues of the galactose α 1,3-galactose target antigens of human antispecies antibodies. Transplant. Proc. 26: 1279–80.PubMedGoogle Scholar
  17. Cairns, T., Lee, J., Goldberg, L., Cook, T., Simpson, P., Spackman, D., Palmer, A., and Taube, D., 1995, Inhibition of the pig to human xenograft reaction, using soluble Galα1–3Gal and Galα1–3Galβl-4GlcNAc. Transplantation. 60: 1202–7.PubMedGoogle Scholar
  18. Cairns, T., Lee, J., Goldberg, L. C., Hakim, N., Cook, T., Rydberg, L., Samuelsson, B., and Taube, D., 1996, Thomsen-Friedenreich and PK antigens in pig-to-human xenotransplantation. Transplant. Proc. 28: 795–6.PubMedGoogle Scholar
  19. Candinas, D., Belliveau, S., Koyamada, N., Miyatake, T., Hechenleitner, P., Mark, W., Bach, F. H., and Hancock, W. W., 1996, T cell independence of macrophage and natural killer cell infiltration, cytokine production, and endothelial activation during delayed xenograft rejection. Transplantation. 62: 1920–7.PubMedGoogle Scholar
  20. Cao, Y., Stosiek, P., Springer. G.F., and Karsten. U., 1996, Thomsen-Friedenreich-related carbohydrate antigens in normal adult human tissues: a systematic and comparative study. Histochem. Cell Biol. 106: 197–207.PubMedGoogle Scholar
  21. Chae, S., Kramer, A.D., Zhao, Y., Arn, J.S., Cooper, D.K.C., and Sachs. D.H. Lack of variation in αGal expression on lymphocytes in miniature swine of different genotypes. (Submitted for publication).Google Scholar
  22. Cohney, S., McKenzie, I. F. C., Patton. K., Prenzoska, J., Ostenreid, K., Fodor, W. L., and Sandrin, M. S., 1997. Down-regulation of Galα(l,3)Gal expression by α1.2-fucosyltransferase: further characterization of α1.2-fucosyltransferase transgenic mice. Transplantation. 64: 495–500.PubMedGoogle Scholar
  23. Collins, B. H., Parker. W., and Platt. J. L., 1994, Characterization of porcine endothelial cell determinants recognized by human natural antibodies. Xenotransplanlation. 1: 36–46.Google Scholar
  24. Cooke, S. P., Hederer, R. A., Pearson, J. D., and Savage. C. O., 1995, Characterization of human IgG-binding xenoantigens expressed by porcine aortic endothelial cells. Transplantation. 60: 1274–84.PubMedGoogle Scholar
  25. Cooper, D. K. C., Human, P. A., Lexer, G., Rose, A. G., Rees. J., Keraan. M., and Du Toit, E., 1988. Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. J. Heart Transplant. 7: 238–246.PubMedGoogle Scholar
  26. Cooper, D.K.C., 1990, A clinical survey of cardiac transplantation between ABO-blood group incompatible recipients and donors. J. Heart Transplant. 9: 376–381.PubMedGoogle Scholar
  27. Cooper, D. K. C., Ye, Y., Rolf. L. L. J.,and Zuhdi, N., 1991, The pig as potential organ donor for man. In: Xenotransplantation. (D.K.C. Cooper. E. Kemp, K. Reemtsma. and D.J.G. White, eds), Springer-Verlag. Heidelberg, pp. 481–500.Google Scholar
  28. Cooper, D. K. C., 1992a, Depletion of natural antibodies in non-human primates-a step towards successful discordant xenografting in humans. Clin. Transplant. 6: 178–183.PubMedGoogle Scholar
  29. Cooper, D. K. C., Ye, Y., Kehoe, M., Niekrasz, M., Rolf. L. J., Martin, M., Baker. J., Kosanke, S., Zuhdi, N., and Worsley, G., et al., 1992b, A novel approach to “neutralization” of preformed antibodies: cardiac allotransplantation across the ABO blood group barrier as a paradigm of discordant transplantation. Transplant. Proc. 24: 566–71.PubMedGoogle Scholar
  30. Cooper, D. K. C. 1993a, Xenografting: how great is the clinical need? Xeno. 1: 25–26.Google Scholar
  31. Cooper, D. K. C., Good. A. H., Koren. E., Oriol. R., Malcolm, A. J., Ippolito. R. M., Neethling, F. A., Ye, Y., Romano, E., and Zuhdi, N., 1993b, Identification of α-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. Transplant. Immunol. 1: 198–205.Google Scholar
  32. Cooper, D. K. C., Good, A. H., Ye, Y., Koren, E., Oriol, R., Ippolito, R. M., Malcolm, A. J., Neethling, F. A., Romano. E., and Zuhdi, N., 1993c, Specific intravenous carbohydrate therapy: a new approach to the inhibition of antibody-mediated rejection following ABO-incompatible allografting and discordant xenografting. Transplant. Proc. 25: 377–378.PubMedGoogle Scholar
  33. Cooper, D. K. C., Koren, E., and Oriol. R., 1993d, Genetically engineered pigs. Lancet. 342:682–3.PubMedGoogle Scholar
  34. Cooper, D. K. C., Ye, Y., Niekrasz, M., Kehoe, M., Martin. M., Neethling, F. A., Kosanke, S., DeBault, L. E., Worsley, G., and Zuhdi, N., et al., 1993e. Specific intravenous carbohydrate therapy. A new concept in inhibiting antibody-mediated rejection—experience with ABO-incompatible cardiac allografting in the baboon. Transplantation. 56: 769–77.PubMedGoogle Scholar
  35. Cooper, D. K. C. Koren, E., and Oriol, R., 1994, Oligosaccharides and discordant xenotransplantation. Immunol. Rev. 141: 31–58.PubMedGoogle Scholar
  36. Cooper, D. K. C., Cairns, T. D. H., and Taube, D. H., 1996a. Extracorporeal immunoadsorption of αGal antibodies. Xeno. 4: 27–29.Google Scholar
  37. Cooper, D. K. C., Koren, E., and Oriol, R., 1996b, Manipulation of the anti-αGal antibody-αGal epitope system in experimental discordant xenotransplantation. Xenotransplantation. 3: 102–111.Google Scholar
  38. Cooper, D. K. C. and Thall, A. D., 1997, Xenoantigens and xenoantibodies: their modification. World J.Surg. 21:901–906.PubMedGoogle Scholar
  39. Cooper, D. K. C., 1998, Xenoantigens and xenoantibodies. Xenotransplantation. 5: 6–17.PubMedGoogle Scholar
  40. Cotterell, A. H., Collins, B. H., Parker, W., Harland, R. C., and Platt, J. L., 1995, The humoral immune response in humans following cross-perfusion of porcine organs. Transplantation. 60:861–8.PubMedGoogle Scholar
  41. Cozzi, E., Yannoutsos, N., Langford, G. A., Pino-Chavez, G., Wallwork, J., and White, D. J. G., 1997, Effect of transgenic expression of human dacay-accelerating factor on the inhibition of hyperacute rejection of pig organs. In: Xenotransplantation, 2nd ed., (D.K.C. Cooper, E. Kemp, J.L. Platt, and D.J.G. White, eds). Springer, Heidelberg, pp. 665–682.Google Scholar
  42. Dalmasso, A. P., Vercellotti, G. M., Platt, J. L., and Bach, F. H., 1991, Inhibition of complement-mediated endothelial cell cytotoxicity by decay-accelerating factor. Potential for prevention of xenograft hyperacute rejection. Transplantation. 52: 530–3.PubMedGoogle Scholar
  43. Dalmasso, A. P., Vercellotti, G. M., Fischel, R. J., Bolman, R. M., Bach, F. H., and Platt, J. L., 1992, Mechanism of complement activation in the hyperacute rejection of porcine organs transplanted into primate recipients. Am. J. Pathol. 140: 1157–66.PubMedGoogle Scholar
  44. Dalmasso, A. P., He, T., and Benson, B. A., 1996, Human IgM xenoreactive natural antibodies can induce resistance of porcine endothelial cells to complement-mediated injury. Xenotransplantation. 3: 54–62.Google Scholar
  45. Davis, E. A., Pruitt, S. K., Greene, P. S., Ibrahim, S., Lam, T. T., Levin, J. L., Baldwin, W. R., and Sanfilippo, F., 1996, Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts. Transplantation. 62: 1018–23.PubMedGoogle Scholar
  46. DeGoma, E., Sykes, M., Thall, A., and Yang, Y-G., 1997, Tolerization of α1,3Gal-specific B cells in lethally irradiated α1,3Gal mice reconstituted with mixed α1,3Gal+ and α1,3Gal BMC. Fourth International Congress for Xenotransplantation. Nantes, France. (Abstract P107).Google Scholar
  47. Dorling, A., Stocker, C., Tsao, T., Haskard, D. O., and Lechler, R. I., 1996. In vitro accommodation of immortalized porcine endothelial cells: resistance to complement mediated lysis and down-regulation of VCAM expression induced by low concentrations of polyclonal human IgG antipig antibodies. Transplantation. 62: 1127–36.PubMedGoogle Scholar
  48. Economidou, J., Hughes, J. N., and Gardner, B., 1967a, The functional activities of IgG and IgM anti-A and anti-B. Immunol. 13: 227–34.Google Scholar
  49. Economidou, J., Hughes, J. N., and Gardner, B., 1967b, Quantitative measurements concerning A and B antigen sites. Vox. Sang. 12: 321–8.PubMedGoogle Scholar
  50. Fischel, R. J., Matas, A. J., Platt, J. L., Perry, E., Noreen, H., Shumway, S. J., and Bolman, R. D., 1992, Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival. J. Heart and Lung Transplant. 11: 965–73.Google Scholar
  51. Fournier, A.M., Birchall, I.E., Kyriazis, A. G., Pearse, M. J., and d’Apice. A. J. F., 1993, A human naturally occurring antibody, anti-Gal, recognizes epitopes in pig kidney, heart, and liver and is cytotoxic to endothelial cells in the presence of rabbit complement. Second International Congress for Xenotransplantation. Cambridge, UK. (Abstract 113).Google Scholar
  52. Galili, U., Rachmr lewitz, E. A., Peleg, A., and Flechner, I., 1984, A unique natural human IgG antibody with anti-α-galactosyl specificity. J. Exp. Med. 160: 1519–31.PubMedGoogle Scholar
  53. Galili, U., Macher, B. A., Buehler, J., and Shohet, S. B., 1985, Human natural anti-α-galactosyl IgG. II. The specific recognition of α(1–3)-linked galactose residues. J. Exp. Med. 162: 573–82.PubMedGoogle Scholar
  54. Galili, U., Buehler, J., Shohet, S. B., and Macher, B. A., 1987a, The human natural anti-Gal IgG. III. The subtlety of immune tolerance in man as demonstrated by crossreactivity between natural anti-Gal and anti-B antibodies. J. Exp. Med. 165: 693–704.PubMedGoogle Scholar
  55. Galili, U., Clark, M. R., Shohet, S. B., Buehler, J., and Macher, B. A., 1987b, Evolutionary relationship between the natural anti-Gal antibody and the Galα1–3Gal epitope in primates. Proc. Natl. Acad. Sci. USA. 84: 1369–73.PubMedGoogle Scholar
  56. Galili, U., Mandrell, R. E., Hamadeh. R. M., Shohet. S. B. and Griffiss. J. M., 1988a. Interaction between human natural anti-α-galactosyl immunoglobulin G and bacteria of the human flora. Infect. Immun. 56: 1730–7.PubMedGoogle Scholar
  57. Galili, U., Shohet, S. B., Kobrin, E., Stults, C. L., and Macher. B. A., 1988b, Man, apes, and Old World monkeys differ from other mammals in the expression of α-galactosyl epitopes on nucleated cells. J. Biol. Chem. 263: 17755–62.PubMedGoogle Scholar
  58. Galili, U., 1991, The natural anti-Gal antibody: evolution and autoimmunity in man. Immunology Series. 55: 355–73.PubMedGoogle Scholar
  59. Galili, U., Anaraki. F., Thall. A., Hill, B. C. and Radic. M., 1993. One percent of human circulating B lymphocytes are capable of producing the natural anti-Gal antibody. Blood. 82: 2485–93.PubMedGoogle Scholar
  60. Galili, U., Tibell. A., Samuelsson. B., Rydberg, L., and Groth. C. G., 1995. Increased anti-Gal activity in diabetic patients transplanted with fetal porcine islet cell clusters. Transplantation. 59: 1549–56.PubMedGoogle Scholar
  61. Galili, U. and Matta, K. L. 1996, Inhibition of anti-Gal IgG binding to porcine endothelial cells by synthetic oligosaccharides. Transplantation. 62: 256–62.PubMedGoogle Scholar
  62. Galili, U., Minanov, O. P., Michler, R. E., and Stone. K. R., 1997, High-affinity anti-Gal immunoglobulin G in chronic rejection of xenografts. Xenotransplantation. 4: 127–131.Google Scholar
  63. Geller, R. L., Bach, F. H., Turman. M. A., Casali, P., and Platt, J. L., 1993. Evidence that polyreactive antibodies are deposited in rejected discordant xenografts. Transplantation. 55: 168–72.PubMedGoogle Scholar
  64. Geller, R. L., Rubinstein, P., and Platt, J. L., 1994. Variation in expression of porcine xenogeneic antigens. Transplantation. 58: 272–7.PubMedGoogle Scholar
  65. Goldberg. L. C. Lee, J., Cairns, T., Weymouth. W. A., Simpson. P., Lawson. C. Hacking, A., Nilsson, R., Hakim. N., and Taube. D., 1996. Polymorphism within the human anti-pig repertoire. Transplant. Proc. 28: 549–50.PubMedGoogle Scholar
  66. Good, A. H., Cooper. D. K. C. Malcolm, A. J., Ippolito, R. M., Koren. E., Neethling, F. A., Ye. Y., Zuhdi, N., and Lamontagne. L. R., 1992. Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. Transplant. Proc. 24: 559–62.PubMedGoogle Scholar
  67. Hendricks. S. P., He. P., Stults, C. L., and Macher. B. A. 1990. Regulation of the expression of Galα 1–3Galβ1–4GlcNAc glycosphingolipids in kidney. J. Biol. Chem. 265: 17621–6.PubMedGoogle Scholar
  68. Holgersson, J., Jovall, P. A., Samuelsson, B. E., and Breimer. M. E., 1990, Structural characterization of non-acid glycosphingolipids in kidneys of single blood group O and A pigs. J. Biochem. 108: 766–77.PubMedGoogle Scholar
  69. Holgersson, J., Cairns. T. D., Karlsson. E. C. Backer. A. E., Breimer. M. E., Taube. D. H., Welsh, K. I., and Samuelsson. B. E., 1992. Carbohydrate specificity of human immunoglobulin-M antibodies with pig lymphocytotoxic activity. Transplant. Proc. 24: 605–8.PubMedGoogle Scholar
  70. Holzknecht, Z. E. and Platt. J. L., 1995. Identification of porcine endothelial cell membrane antigens recognized by human xenoreactive natural antibodies. J. Immunol. 154: 4565–75.PubMedGoogle Scholar
  71. Inverardi, L. and Pardi, R., 1994, Early events in cell-mediated recognition of vascularized xenografts: cooperative interactions between selected lymphocyte subsets and natural antibodies. [Review] [56 refs]. Immunol. Rev. 141: 71–93.PubMedGoogle Scholar
  72. Inverardi, L., Clissi. B., Stolzer. A. L., Bender. J. R., Sandrin. M. S., and Pardi. R., 1997. Human natural killer lymphocytes directly recognize evolutionary conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation. 63: 1318–30.PubMedGoogle Scholar
  73. Itescu, S., Kwiatkowski, P., Wang, S. F., Blood, T., Minanov. P., Rose, S., and Michler, R. E., 1996, Circulating human mononuclear cells exhibit augmented lysis of pig endothelium after activation with interleukin 2. Transplantation. 62: 1927–33.PubMedGoogle Scholar
  74. Itescu, S., Minanov, O. P., and Michler, R. E., 1997. Newborn pig-to-baboon cardiac xenotransplantation: a model of delayed xenograft rejection. In: Xenotransplantation, 2nd ed., (D.K.C. Cooper, E. Kemp, J.L. Platt, and D.J.G. White, eds), Springer, Heidelberg, pp. 478–487.Google Scholar
  75. Joziasse, D. H., Shaper, J. H., Van den, Eijnden, Dh, Van, T. A., and Shaper, N. L., 1989, Bovine α1–3-galactosyltransferase: isolation and characterization of a cDN A clone. Identification of homologous sequences in human genomic DNA. J. Biol. Chem. 264: 14290–7.PubMedGoogle Scholar
  76. Joziasse, D. H., Shaper, J. H., Jabs, E. W., and Shaper, N. L., 1991, Characterization of an α 1–3-galactosyltransferase homologue on human chromosome 12 that is organized as a processed pseudogene. J. Biol. Chem. 266: 6991–8.PubMedGoogle Scholar
  77. Kaplon, R. J., Michler, R. E., Xu, H., Kwiatkowski, P. A., Edwards, N. M., and Platt, J. L., 1995, Absence of hyperacute rejection in newborn pig-to-baboon cardiac xenografts. Transplantation. 59: 1–6.PubMedGoogle Scholar
  78. Karlsson, E., Cairns, T., Holgersson, J., Welsh, K., and Samuelsson, B., 1993, Pig to human xenotransplantation. Confirmation of the major target epitope of pre-formed human natural IgG and IgM anti-pig-teminal galactose 1,3 galactose. Clycoconjugate J. 10: 297.Google Scholar
  79. Katayama, A., Ogawa, H., Kadomatsu, K., Kurosawa, N., Kobayashi, T., Kaneda, N., Uchimura, K., Yokoyama, I., Muramatsu, T., and Takagi, H., 1998, Porcine α1,3-galactosyltransferase: full length cDN A cloning, genomic organization, and analysis of splicing variants. Glycoconjugate J. (In press).Google Scholar
  80. Kobayashi, T., Neethling, F. A., Taniguchi, S., Ye, Y., Niekrasz, M., Koren, E., Hancock, W. W., Takagi, H., and Cooper, D. K. C., 1996, Investigation of the anti-complement agents, FUT-175 and K76COOH, in discordant xenotransplantation. Xenotransplantation. 3: 237–245.Google Scholar
  81. Kobayashi, T., Taniguchi, S., Neethling, F. A., Rose, A. G., Hancock, W. W., Ye, Y., Niekrasz, M., Kosanke, S., Wright, L. J., White, D. J. G., and Cooper, D. K. C., 1997, Delayed xenograft rejection of pig-to-baboon cardiac transplants after cobra venom factor therapy. Transplantation. 64: 1255–1261.PubMedGoogle Scholar
  82. Koike, C., Kannagi, R., Takuma, Y., Akutsu, F., Hayashi, S., Hiraiwa, N., Kadomatsu, K., Yamakawa, H., Nagai, T., Kobayashi, S., Okada, H., Nakashima, I., Uchida, K., Yokoyama, l., and Takagi, H., 1996, Introduction of ( l,2)-fucosyltransferase and its effect on α-Gal epitopes in transgenic pig. Xenotransplantation. 3: 81–86.Google Scholar
  83. Kooyman, D. L., McClellan, S. B., Parker, W., Avissar, P. L., Velardo, M. A., Platt, J. L., and Logan, J. S., 1996, Identification and characterization of a galactosyl peptide mimetic. Implications for use in removing xenoreactive anti-A Gal antibodies. Transplantation. 61: 851–5.PubMedGoogle Scholar
  84. Koren, E., Neethling, F. A., Ye, Y., Niekrasz, M., Baker, J., Martin, M., Zuhdi, N., and Cooper, D. K. C., 1992, Heterogeneity of preformed human antipig xenogeneic antibodies. Transplant. Proc. 24:598–601.PubMedGoogle Scholar
  85. Koren, E., Neethling, F. A., Richards, S., Koscec, M., Ye, Y., Zuhdi, N., and Cooper, D. K. C., 1993, Binding and specificity of major immunoglobulin classes of preformed human anti-pig heart antibodies. Transplant. Int. 6: 351–3.Google Scholar
  86. Koren, E., Kujundzic, M., Koscec, M., Neethling, F. A., Richards, S. V., Ye, Y., Zuhdi. N., and Cooper, D. K. C., 1994, Cytotoxic effects of human preformed anti-Gal IgG and complement on cultured pig cells. Transplant. Proc. 26: 1336–9.PubMedGoogle Scholar
  87. Koren, E., Milotic, F., Neethling, F. A., Koscec, M., Fei, D., Kobayashi, T., Taniguchi, S., and Cooper, D. K. C., 1996, Monoclonal antiidiotypic antibodies neutralize cytotoxic effects of anti-αGal antibodies. Transplantation. 62: 837–43.PubMedGoogle Scholar
  88. Kozlowski, T., Fuchimoto, Y., Monroy, R., Bailin, M., Martinez, R. R., Foley, A., Xu, Y., Awwad, M., Fishman, J., Andrews, D., Ritzenthaler, J., Sablinski, T., Ierino, F. L., and Sachs, D. H., 1997, Apheresis and column absorption for specific removal of Gal-α-1,3 Gal natural antibodies in a pig-to-baboon model. Transplant. Proc. 29: 961–962.PubMedGoogle Scholar
  89. Kozlowski, T., Monroy, R., Xu, Y., Glaser, R., Awwad. M., Cooper. D.K.C., and Sachs, D.H., 1998. Anti-αGal antibody response to porcine bone marrow in unmodified baboons and baboons conditioned for tolerance induction. Transplantation. (In pressl.Google Scholar
  90. Kroshus, T. J., Bolman, R. R., and Dalmasso. A. P., 1996. Selective IgM depletion prolongs organ survival in an ex vivo model of pig-to-human xenotransplantation. Transplantation. 62: 5–12.PubMedGoogle Scholar
  91. Kujundzic, M., Koren, E., Neethling, F. A., Milotic. F., Koscec. M., Kujundzic. T., Martin. M., and Cooper, D. K. C., 1994. Variability of anti-αGal antibodies in human serum and their relation to serum cytotoxicity against pig cells. Xenotransplantation. 1: 58–65.Google Scholar
  92. Lambrigts, D., Van Calster, P., Xu. X., Awwad. M., Neethling, F.A., Kozlowski, T., Foley, A., Watts, A., Chae, S., Thall. A., White-Scharf, M., Sachs. D.H., and Cooper. D.K.C., 1998, Pharmacologic immunosuppressive therapy and extracorporeal immunoadsorption in the suppression of anti-αGal antibody in the baboon. (Submitted for publication).Google Scholar
  93. Larsen, R. D., Rajan, V. P., Ruff, M. M., Kukowska. L. J., Cummings. R. D., and Lowe, J. B., 1989, Isolation of a cDNA encoding a murine UDP galactoseiβ-D-galactosyl-α-1,4-N-acetyl-D-glucosaminide α-1.3-galactosyltransferase: expression cloning by gene transfer. Proc. Satl. Acad. Sci. USA. 86: 8227–31.Google Scholar
  94. Larsen. R. D., Rivera, M. C., Ernst, L. K., Cummings, R. D., and Lowe. J. B., 1990, Frameshift and nonsense mutations in a human genomic sequence homologous to a murine UDP-Gal:β-D-Gal(1.4)-D-GlcNAca(1.3)-galactosyltransferase cDNA. J. Biol. Chem. 265: 7055–61.PubMedGoogle Scholar
  95. Latinne, D., Gianello, P., Smith, C. V., Nickeleit. V., Kawai. T., Beadle. M., Haug, C., Sykes, M., Lebowitz, E., and Bazin, H., et al., 1993, Xenotransplantation from pig to cynomolgus monkey: approach toward tolerance induction. Transplant. Proc. 25: 336–8.PubMedGoogle Scholar
  96. Latinne, D., Soares, M., Havaux, X., Cormont, F., Lesnikoski, B., Bach. F. H., and Bazin. H., 1994. Depletion of IgM xenoreactive natural antibodies by injection of anti-mu monoclonal antibodies. Immunol. Rev. 141: 95–125.PubMedGoogle Scholar
  97. LaVecchio. J. A., Dunne. A. D., and Edge. A. S., 1995. Enzymatic removal of α-galactosyl epitopes from porcine endothelial cells diminishes the cytotoxic effect of natural antibodies. Transplantation. 60: 841–7.Google Scholar
  98. Leventhal. J. R., Dalmasso. A. P., Cromwell. J. W., Platt. J. L., Manivel. C. J., Bolman. R. D., and Matas. A. J., 1993. Prolongation of cardiac xenograft survival by depletion of complement. Transplantation. 55: 857–65.PubMedGoogle Scholar
  99. Leventhal, J. R., John, R., Fryer. J. P., Witson. J. C., Derlich, J. M., Remiszewski, J., Dalmasso, A. P., Matas, A. J., and Bolman, R. R., 1995. Removal of baboon and human antiporcine IgG and IgM natural antibodies by immunoadsorption. Results of in vitro and in vivo studies. Transplantation. 59: 294–300.PubMedGoogle Scholar
  100. Lexer, G., Cooper, D.K.,C. Rose. A.G., Wicomb. W.N., Rees. J., Keraan, M., and du Toit, E., 1986. Hyperacute rejection in a discordant (pig-to-baboon) cardiac xenograft model. J. Heart Transplant. 5:411–8.PubMedGoogle Scholar
  101. Li, S. F., Neethling, F. A., Taniguchi. S., Yeh. J. C. Kobayashi. T., Ye. Y., Koren. E., Cummings. R. D., and Cooper, D. K. C. 1996. Glycans derived from porcine stomach mucin are effective inhibitors of natural anti-α-galactosyl antibodies in vitro and after intravenous infusion in baboons. Transplantation. 62: 1324–31.PubMedGoogle Scholar
  102. Li, S., Yeh, J-C, Cooper, D.K.C., and Cummings, R.D., 1995. Inhibition of human anti-αGal IgG by oligosaccharides derived from porcine stomach mucin. Xenotransplantation. 2: 279–278.Google Scholar
  103. Lin, Y., Vandeputte, M., and Waer. M., 1997, Contribution of activated macrophages to the process of delayed xenograft rejection. Transplantation. 64: 1677–1683.PubMedGoogle Scholar
  104. Liu, J., Qian, Y., and Holgersson, J., 1997. Removal of xenoreactive human anti-pig antibodies by absorption on recombinant mucin-containing glycoproteins carrying the Gal α1,3Gal epitope. Transplantation. 63: 1673–82.PubMedGoogle Scholar
  105. Lucisano Valim, Y. M. and Lachmann, P. J., 1991, The effect of antibody isotype and antigenic epitope density on the complement-fixing activity of immune complexes: a systematic study using chemaeric anti-NIP antibodies with human Fc regions. Clin. Exp. Immunol. 84: 1–8.PubMedGoogle Scholar
  106. Luo, Y., Cummings, R., Cooper, D. K. C., Katz, E., and Zuhdi, N., 1997, Green coffee bean α-galactosidase: its working condition and potential application in xenotransplantation. Fourth International Congress for Xenotransplantation. Nantes, France. (Abstract Pl 06).Google Scholar
  107. McKenzie, I. F. C., Xing, P. X., Vaughan, H. A., Prenzoska, J., Dabkowski, P. L., and Sandrin, M. S., 1994, Distribution of the major xenoantigen (galα1–3gal) for pig to human xenografts. Transplant. Immunol. 2: 81–6.Google Scholar
  108. McMorrow, I. M., Comrack, C. A., Nazarey, P. P., Sachs, D. H., and DerSimonian, H., 1997a, Relationship between ABO blood group and levels of aGα1,3galactose-reactive human immuno-globulin G. Transplantation. 64: 546–549.PubMedGoogle Scholar
  109. McMorrow, I. M., Comrack, C. A., Sachs, D. H., and DerSimonian, H., 1997b, Heterogeneity of human anti-pig natural antibodies cross-reactive with the αGal(l,3)Galactose epitope. Transplantation. 64: 501–510.PubMedGoogle Scholar
  110. Minanov, O. P., Itescu, S., Neethling, F. A., Morgenthau, A. S., Kwiatkowski, P., Cooper, D. K. C., and Michler, R. E., 1997, Anti-GaL IgG antibodies in sera of newborn humans and baboons and its significance in pig xenotransplantation. Transplantation. 63: 182–6.PubMedGoogle Scholar
  111. Nagasaka, T., Kobayashi, T., Muramatsu, H., Fujimoto, H., Matsuo, I., Ajisaka, K., Kadomatsu, K., Hayashi, S., Yokoyama, I., Hayakawa, A., Muramatsu, T., and Takagi, H., 1997, α-Galactosyl oligosaccharides conjugated with polyethylene glycol as potential inhibitors of hyperacute rejection upon xenotransplantation. Bioehem. Biophvs. Res. Comm. 232: 731–6.Google Scholar
  112. Neethling, F.A. and Cooper, D.K.C., 1998, A comparison of the variability and specificity of anti-αGal antibodies in baboons and humans. (Submitted for publication).Google Scholar
  113. Neethling, F. A., Koren, E., Ye, Y., Richards, S. V., Kujundzic. M., Oriol, R., and Cooper, D. K. C., 1994, Protection of pig kidney (PK15) cells from the cytotoxic effect of anti-pig antibodies by α-galactosyl oligosaccharides. Transplantation. 57: 959–63.PubMedGoogle Scholar
  114. Neethling, F. A., Joziasse, D., Bovin, N., Cooper, D. K. C., and Oriol, R., 1996, The reducing end of αGal oligosaccharides contributes to their efficiency in blocking natural antibodies of human and baboon sera. Transplant. Int. 9: 98–101.Google Scholar
  115. Okada, H. and Tanaka, H., 1983 Species-specific inhibition by glycophorins of complement activation via the alternative pathway. Molecular Immunol. 20: 1233–6.Google Scholar
  116. Oriol, R., Le, P. J., and Mollicone, R., 1986, Genetics of ABO, H, Lewis, X and related antigens. Vox. Sang. 51: 161–71.PubMedGoogle Scholar
  117. Oriol, R., Ye, Y., Koren, E., and Cooper, D. K. C., 1993, Carbohydrate antigens of pig tissues reacting with human natural antibodies as potential targets for hyperacute vascular rejection in pig-toman organ xenotransplantation. Transplantation. 56: 1433–42.PubMedGoogle Scholar
  118. Oriol, R., Barthod, F., Bergemer, A. M., Ye, Y., Koren, E., and Cooper, D. K. C., 1994, Monomorphic and polymorphic carbohydrate antigens on pig tissues: implications for organ xenotransplantation in the pig-to-human model. Transplant. Int. 7: 405–13.Google Scholar
  119. Palmer, A., Taube, D., Welsh, K., Bewick, M., Gjorstrup, P., and Thick, M., 1989, Removal of anti-HLA antibodies by extracorporeal immunoadsorption to enable renal transplantation. Lancet. 1: 10–2.PubMedGoogle Scholar
  120. Parker, W., Bruno, D., Holzknecht, Z. E., and Platt, J. L., 1994, Characterization and affinity isolation of xenoreactive human natural antibodies. J. Immunol. 153: 3791–803.PubMedGoogle Scholar
  121. Parker, W., Lateef, J., Everett, M. L., and Platt, J. L., 1996a, Specificity of xenoreactive anti-Galα1–3Gal igM for α-galactosyl ligands. Glycobiol. 6: 499–506.Google Scholar
  122. Parker, W., Saadi, S., Lin, S. S., Holzknecht, Z. E., Bustos, M., and Platt, J. L., 1996b, Transplantation of discordant xenografts: a challenge revisited. [Review] [53 refs]. Immunol. Today. 17: 373–8.PubMedGoogle Scholar
  123. Pascher, A., Poehlein, C., Stangl, M., Hoebel, G., Thiery. J., Mueller, D. J., and Hammer, C., 1997, Application of immunoapheresis for delaying hyperacute rejection during isolated xenogeneic pig liver perfusion. Transplantation, 63: 867–75.PubMedGoogle Scholar
  124. Perper, R. J. and Najarian, J. S., 1966a, Experimetal renal heterotransplantaion 1. in widely divergent species. Transplantation. 4: 377–388.PubMedGoogle Scholar
  125. Perper, R. J. and Najarian, J. S., 1966b, Experimental renal heterotransplantation II. closely related species. Transplantation. 4: 700–712.PubMedGoogle Scholar
  126. Platt, J. L., Lindman, B. J., Chen. H., Spitalnik. S. L., and Bach. F. H., 1990, Endothelial cell antigens recognized by xenoreactive human natural antibodies. Transplantation. 50: 817–22.PubMedGoogle Scholar
  127. Platt, J. L., Fischel, R. J., Matas. A. J., Reif. S. A., Bolman. R. M., and Bach, F. H., 1991. Immunopathology of hyperacute xenograft rejection in a swine-to-primate model. Transplantation. 52: 214–20.PubMedGoogle Scholar
  128. Platt, J. L. and Holzknecht, Z. E., 1994, Porcine platelet antigens recognized by human xenoreactive natural antibodies. Transplantation. 57: 327–35.PubMedGoogle Scholar
  129. Platt, J. L. and Logan. J. S., 1997, Use of transgenic animals as xenotransplant donors. In: Xenotransplantation, 2nd ed., (D.K.C. Cooper. E. Kemp. J.L. Platt, and D.J.G. White, eds). Springer, Heidelberg, pp. 650–658.Google Scholar
  130. Raja. R., McAlack, R., Mendez. M., and Bannett. A., 1987. Technical aspects of antibody immunoadsorptionpriortoABO-incompatiblerenaltransplant. Transplant. Proc. 19:4525–7.PubMedGoogle Scholar
  131. Ratner, A. J., Canhui, H., Pepino. P., Sanchez. J. A., Edwards. N., Watkins. J. F., Xu, H., Reemtsma. K., Rose, E. A., and Berger. C., 1992. Lymphocyte xenoantigens recognized by preformed antibodies. Transplant. Proc. 24: 583–5.PubMedGoogle Scholar
  132. Rieben, R., von Allmen, E., Korchagina. E. Y., Nydegger, U. E., Neethling, F. A., Kujundzic, M., Koren, E., Bovin. N. V., and Cooper, D. K. C., 1995. Detection, immunoabsorption. and inhibition of cytotoxic activity of anti-αGal antibodies using newly developed substances with synthetic Galα1–3Gal disaccharide epitopes. Xenotransplantation. 2: 98–106.Google Scholar
  133. Roelcke, D., 1989, Cold agglutination. Transfusion Med. Rev. 3: 140–66.Google Scholar
  134. Rollins, S. A., Zhao, J., Ninomiya, H., and Sims. P. J., 1991. Inhibition of homologous complement by CD59 is mediated by a species-selective recognition conferred through binding to C8 within C5b-8 or C9 within C5b-9. J. Immunol. 146: 2345–51.PubMedGoogle Scholar
  135. Romano, E., Neethling. F.A., Nilsson. K., Magnusson. S., Svensson. L., Samuelsson, B., and Cooper, D.K.C, 1998, Intravenous synthetic αGal saccharides delay hyperacute rejection of a pig-to-baboon heart transplant. (Submitted for publication).Google Scholar
  136. Roslin, M. S., Zisbrod, Z., Burack, J. H., Tranbaugh, R. F., Strashun, A., Jacobowitz. I. J., Brewer, R. J., Kim, Y., Cunningham, J. N., and Norin, A. J., 1992, 15-day survival in pig-to-baboon heterotopic cardiac xenotransplantation. Transplant. Proc. 24: 572–3.PubMedGoogle Scholar
  137. Ross, J. R., Kirk, A. D., Ibrahim, S. E., Howell, D. N., Baldwin, W. D., and Sanfilippo, F. P., 1993, Characterization of human anti-porcine “natural antibodies” recovered from ex vivo perfused hearts—predominance of IgM and IgG2. Transplantation. 55: 1144–50.PubMedGoogle Scholar
  138. Rydberg, L., Cairns, T. D. H., Groth, C. G., Gustavsson, M. L., Karlsson, E. C., Moller, E., Satake, M., Tibell, A., and Samuelsson. B. E., 1994. Specificities of human IgM and IgG anticarbohydrate xenoantibodies found in the sera of diabetic patients grafted with fetal pig islets. Xenotransplantation. 1: 69–79.Google Scholar
  139. Rydberg, L., Hallberg, E., Bjorck, S., Magnusson, S., Strokan. V., Samuelsson. B. E., and Breimer, M. E., 1995, Studies on the removal of anti-pig xenoantibodies in the human by plasmapheresis/immunoadsorption. Xenotransplantation. 2: 253–263.Google Scholar
  140. Rydberg, L., Bjorck, S., Hallberg, E., Magnusson, S., Sumitran, S., Samuelsson, B. E., Strokan, V., Svalander, C. T., and Breimer, M. E., 1996, Extracorpreal (“ex vivo”) connection of pig kidneys to humans. II. The anti-pig antibody response. Xenotransplantation. 3: 340–353.Google Scholar
  141. Sablinski, T., Latinne, D., Gianello, P., Bailin, M., Bergen, K., Colvin, R. B., Foley, A., Hong, H.-Z., Lorf, T., Meehan, S., Monroy, R., Powelson, J. A., Sykes, M., Tanaka, M., Cosimi, A. B., and Sachs, D. H., 1995, Xenotransplantation of pig kidneys to nonhuman primates: 1. Development of the model. Xenotransplantation. 2: 264–270.Google Scholar
  142. Sablinski, T., Gianello, P. R., Bailin, M., Bergen, K. S., Emery, D. W., Fishman, J. A., Foley, A., Hatch, T., Hawley, R. J., Kozlowski, T., Lorf, T., Meehan, S., Monroy, R., Powelson, J. A., Colvin, R. B., Cosimi, A. B., and Sachs, D. H., 1997, Pig to monkey bone marrow and kidney xenotransplantation. Surgery. 121: 381–91.PubMedGoogle Scholar
  143. Samuelsson, B. E., Rydberg, L., Breimer, M. E., Backer, A., Gustavsson, M., Holgersson, J., Karlsson, E., Uyterwaal, A. C., Cairns, T., and Welsh, K., 1994, Natural antibodies and human xenotransplantation. Immunol. Rev. 141: 151–68.PubMedGoogle Scholar
  144. Sandrin, M. S., Vaughan, H. A., Dabkowski, P. L., and McKenzie, I. F. C., 1993, Anti-pig IgM antibodies in human serum react predominantly with Gal(α1–3)Gal epitopes. Proc. Natl. Acad. Sci. USA. 90: 11391–5.PubMedGoogle Scholar
  145. Sandrin, M. S., Dabkowski, P. L., Henning, M. M., Mouhtouris, E., and McKenzie. I. F. C., 1994, Characterization of cDNA clones for porcine ( 1,3)galactosyltransferase: The enzyme generating the Gal(l,3)Gal epitope.Xenotransplantation. 1: 81–88.Google Scholar
  146. Sandrin, M. S., Fodor, W. L., Mouhtouris, E., Osman, N., Cohney, S., Rollins, S. A., Guilmette, E. R., Setter, E., Squinto, S. P., and McKenzie, I. F. C., 1995, Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nature Med. 1: 1261–7.PubMedGoogle Scholar
  147. Sandrin, M. S., Cohney, S., Osman, N., and McKenzie, l. F. C., 1997, Overcoming the anti-Gal(1–3)Gal reaction to avoid hyperacute rejection: molecular genetic approaches. In: Xenotransplantation, 2nd ed., (D.K.C. Cooper, E. Kemp, J.L. Platt, and D.J.G. White, eds), Springer, Heidelberg, pp. 683–700.Google Scholar
  148. Satake, M., Kawagishi, N., Rydberg, L., Samuelsson, B. E., Tibell, A., Groth, C. G., and Moller, E., 1994, Limited specificity of xenoantibodies in diabetic patients transplanted with fetal porcine islet cell-linked galactose-containing epitopes. Xenotransplantation. 1: 89–101.Google Scholar
  149. Schaapherder, A. F., Daha, M. R., te, B. M., van der, Woude, Fj, and Gooszen, H. G., 1994, Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation. 57: 1376–82.PubMedGoogle Scholar
  150. Schaapherder, A. F., Gooszen, H. G., te, B. M., and Daha, M. R., 1995, Human complement activation via the alternative pathway on porcine endothelium initiated by IgA antibodies. Transplantation. 60: 287–91.PubMedGoogle Scholar
  151. Seebach, J. D., Yamada, K., McMorrow, I. M. Sachs, D. H., and DerSimonian, H. D., 1996, Xenogeneic human anti-pig cytotoxicity mediated by activated natural killer cells. Xenotransplantation. 3: 188–197.Google Scholar
  152. Seebach, J. D. and Waneck, G. L., 1997, Natural killer cells in xenotransplantation. Xenotransplantation. 4: 201–211.Google Scholar
  153. Seya, T., Okada, M., Hazeki, K., and Nagasawa, S., 1990, Regulatory system of guineα-pig complement C3b: two factor I-cofactor proteins on guineα-pig peritoneal granulocytes. Biochem. Biophys. Res. Com. 170: 504–12.PubMedGoogle Scholar
  154. Sharma, A., Okabe, J., Birch, P., McClellan, S. B., Martin, M. J., Platt, J. L., and Logan, J. S., 1996, Reduction in the level of Gal(α1,3)Gal in transgenic mice and pigs by the expression of an α(l,2)fucosyltransferase. Proc. Natl. Acad. Sci. USA. 93: 7190–5.PubMedGoogle Scholar
  155. Sharma, A., Okabe, J., Birch, P., McClellan, S., Martin, M., Platt, J. L., and Logan, J. S., 1997, Downregulation of the Gal epitope in transgenic mice and pigs by expression of 1,2 fucosyltransferase or 2,6 sialyltransferase. Fourth International Congress for Xenotransplantation. Nantes, France. (Abstract 029).Google Scholar
  156. Shinkel, T.A., Chen, C-J., Salvaris. E., Henion. T.R., Barlow. H., Galili, U., Pearse, M.J., and d’Apice. A.J.F., 1997, Changes in cell surface glycosylation in α1,3-galactosyltransferase knock-out and αl,2-fucosyltransferase transgenic mice. Transplantation. 64: 197–204.PubMedGoogle Scholar
  157. Siegel, J. B., Grey, S. T., Lesnikoski. B.-A., Kopp. C. W., Soares. M., am Esch. J. S., Bach, F. H., and Robson, S. C., 1997, Xenogeneic endothelial cells activate human prothrombin. Transplantation. 64: 888–896.PubMedGoogle Scholar
  158. Simon, P. M., Neethling. F. A., Taniguchi. S., Goode. P. L., Zopf. D., Hancock. W. W., and Cooper. D. K. C., 1998. Intravenous infusion of αGal oligosaccharides in baboons delays hyperacute rejeciton of porcine heart xenografts. Transplantation. 63: 346–353.Google Scholar
  159. Squinto, S. P. and Fodor. W. L., 1997. Engineering of xenografts to provide organs for human transplantation. In: Xenotransplantation, 2nd ed., (D.K.C. Cooper. E. Kemp. J.L. Platt, and D.J.G. White, eds), Springer, Heidelberg, pp. 659–664.Google Scholar
  160. Strahan, K. M., Gu, F., Preece. A. F., Gustavsson. I., Andersson. L., and Gustafsson. K., 1995. cDNA sequence and chromosome localization of pig α1.3 galactosyltransferase. Immunogenet. 41: 101–5.Google Scholar
  161. Tachi, Y., Kobayashi, T., Yokoyama, I., Hayashi. S., Negita. M., Namii, Y., Katayatna, A., Nagasaka. T., Mei. G.-L, Hayakawa. A., Matsuda. H., Muramatsu. T., and Takagi. H., 1998. Variability fo cytotoxicity to pig cultured cells and its determinant factors in human sera. Transplant. Proc. 30:71–3.PubMedGoogle Scholar
  162. Takizawa, H., Takahashi, K., Murakami. T., Okada, N., and Okada. H., 1992, Species-specific restriction of complement by HRF20 (CD59) generated by cDNA transfection. Eur. J. Immunol. 22: 1943–6.PubMedGoogle Scholar
  163. Tanemura, M., Miyagawa. S., Ihara. Y., Matsuda. H., Shirakura, R., and Taniguchi, N., 1997a, Significant downregulation of the major swine xenoantigen by N-acetylglucosaminyltransferase 111 gene transfection. Biochem. Biophys. Res. Com. 235: 359–64.PubMedGoogle Scholar
  164. Tanemura, M., Miyagawa. S., Ihara. Y., Matsuda, H., Tsuji, S., Shirakura, R., and Taniguchi. N., 1997b, Coexpression of N-acetylglucosaminyltransferase III (GnT-III) and 2,3 sialyltransferase (2,3 ST) gene for reduciton of xenoantigens. Fourth International Congress for Xenotransplantation. Nantes. France. (Abstract 069).Google Scholar
  165. Tange, M. J., Pearse. M. J., and d’ Apice. A. J. F., 1997a. Galα1–3Gal xenoepitope: donor-targeted genetic strategies. In: Xenotransplantation, 2nd ed., (D.K.C. Cooper, E. Kemp, J.L. Platt, and D.J.G. White, eds). Springer. Heidelberg, pp. 701–713.Google Scholar
  166. Tange, M. J., Tearle, R. G., Aminian, A., Romanella, M., Adam. W. R., Pearse, M. J., and d’Apice, A. J. F., 1997b, Demonstration of the functional importance of the Gal epitope in an ex vivo model of xenotransplantation. Xenotransplantation. 4: 20–24.Google Scholar
  167. Taniguchi, S. and Cooper, D.K.C, 1997, Clinical xenotransplantation—past, present and future. Ann. R. Coll.Surg. Engl. 79: 13–19.PubMedGoogle Scholar
  168. Taniguchi, S., Kobayashi, T., Neethling, F. A., Ye, Y., Niekrasz, M., White, D. J., and Cooper, D.K.C, 1996a, Cobra venom factor stimulates anti-α-galactose antibody production in baboons. Implications for pig-to-human xenotransplantation. Transplantation. 62: 678–81.PubMedGoogle Scholar
  169. Taniguchi, S., Neethling, F. A., Korchagina. E. Y., Bovin. N., Ye. Y., Kobayashi. T., Niekrasz. M., Li. S., Koren. E., Oriol. R., and Cooper. D. K. C. 1996b. In vivo immunoadsorption of antipig antibodies in baboons using a specific Galα1–3Gal column. Transplantation 62: 1379–84.PubMedGoogle Scholar
  170. Tearle, R. G., Tange, M. J., Zannettino. Z. L., Katerelos, M., Shinkel. T. A., Van. D. B., Lonie, A. J., Lyons, I., Nottle. M. B., Cox. T., Becker. C., Peura. A. M., Wigley, P. L., Crawford, R. J., Robins, A. J., Pearse, M. J., and d’Apice, A. J., 1996, The α-1,3-galactosyltransferase knockout mouse. Implications for xenotransplantation. Transplantation. 61: 13–9.PubMedGoogle Scholar
  171. Thall, A. D., Maly, P., and Lowe, J. B., 1995, Oocyte Gal α1,3Gal epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse. J. Biol. Chem. 270: 21437–40.PubMedGoogle Scholar
  172. Thibaudeau, K., Anegon, I., Lemauff, B., Soulillou, J. P., and Blanchard, D., 1994, Human natural antibodies to porcine platelets. Transplantation. 57: 1110–5.PubMedGoogle Scholar
  173. Toma, H., 1994, ABO-incompatible renal transplantation. Urologic Clinics of North America. 21: 299–310.PubMedGoogle Scholar
  174. Turman, M. A., Casali, P., Notkins, A. L., Bach, F. H., and Platt, J. L., 1991, Polyreactivity and antigen specificity of human xenoreactive monoclonal and serum natural antibodies. Transplantation. 52:710–7.PubMedGoogle Scholar
  175. Tuso, P. J., Cramer, D. V., Middleton, Y. D., Kearns, J. M., Yasunaga, C., Cosenza, C. A., Davis, W. C., Wu, G. D., and Makowka, L., 1993, Pig aortic endothelial cell antigens recognized by human IgM natural antibodies. Transplantation. 56: 651–5.PubMedGoogle Scholar
  176. Vanhove, B. and Bach, F. H., 1993, Human xenoreactive natural antibodies—avidity and targets on porcine endothelial cells. Transplantation. 56: 1251–3.PubMedGoogle Scholar
  177. Vanhove, B., Charreau, B., Cassard, A., Soulillou, J. P., and Pourcel, C., 1997a, α1,3 galactosyltransferase inhibition in the pig: a new approach. Fourth International Congress for Xenotransplantation. Nantes, France. (Abstract 040).Google Scholar
  178. Vanhove, B., Goret, F., Soulillou, J. P., and Pourcel, C., 1997b, Porcine α 1,3-galactosyltransferase: tissue-specific and regulated expression of splicing isoforms. Biochem. Biophys. Acta. 1356: 1–11.PubMedGoogle Scholar
  179. Vaughan, H. A., Loveland, B. E., and Sandrin, M. S., 1994, Gal α(1,3)Gal is the major xenoepitope expressed on pig endothelial cells recognized by naturally occurring cytotoxic human antibodies. Transplantation. 58: 879–82.PubMedGoogle Scholar
  180. Vaughan, H. A., McKenzie, I. F. C., and Sandrin, M. S., 1995, Biochemical studies of pig xenoantigens detected by naturally occurring human antibodies and the galactose α(1–3)galactose reactive lectin. Transplantation. 59: 102–9.PubMedGoogle Scholar
  181. Vaughan, H. A., Oldenburg, K. R., Gallop, M. A., Atkin, J. D., McKenzie, l. F. C., and Sandrin, M. S., 1996, Recognition of an octapeptide sequence by multiple Galα(l,3)Gal-binding proteins. Xenotransplantation. 3: 18–23.Google Scholar
  182. Watier, H., Guillaumin, J. M., Piller, F., Lacord, M., Thibault, G., Lebranchu, Y., Monsigny, M., and Bardos, P., 1996, Removal of terminal alphα-galactosyl residues from xenogeneic porcine endothelial cells. Decrease in complement-mediated cytotoxicity but persistence of IgGl-mediated antibody-dependent cell-mediated cytotoxicity. Transplantation. 62: 105–13.PubMedGoogle Scholar
  183. Wieslander, J., Mansson, O., Kallin, E., Gabrielli, A., Nowack, H., and Timpl, R., 1990, Specificity of human antibodies against Galα1–3Gal carbohydrate epitope and distinction from natural antibodies reacting with Galαl-2Gal or Galα1–4Gal. Glycoconjugate J. 7: 85–100.Google Scholar
  184. Weiss, R. A., 1998, Transgenic pigs and virus adaptation. Nature. 391: 327–328.PubMedGoogle Scholar
  185. Xu, Y., Lorf, T., Sablinski, T., Gianello, P., Bailin, M., Monroy. R., Kozlowski, T., Cooper, D.K.C., and Sachs, D.H., 1998, Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Galα1–3Galβl-4βGlc-X immunoaffinity column. Transplantation. 65: 172–179.PubMedGoogle Scholar
  186. Xu, H., Kwiatkowski, P., Chen. J. M., Kaplon, R. J., Edwards, N. M., Dong, X., Berger, C., and Michler, R. E., 1994, Abrogation of baboon natural xenoantibody to pig splenocytes by DL-penicillamine. Transplantation. 58: 1299–303.PubMedGoogle Scholar
  187. Ye, Y., Niekrasz, M., Kosanke, S., Welsh, R., Jordan, H. E., Fox, J. C., Edwards, W. C., Maxwell, C., and Cooper, D. K. C., 1994a, The pig as a potential organ donor for man. A study of potentially transferable disease from donor pig to recipient man. Transplantation. 57: 694–703.PubMedGoogle Scholar
  188. Ye, Y., Neethling, F. A., Niekrasz, M., Koren, E., Richards, S. V., Martin, M., Kosanke, S., Oriol, R., and Cooper, D. K. C., 1994b, Evidence that intravenously administered α-galactosyl carbohydrates reduce baboon serum cytotoxicity to pig kidney cells (PK15) and transplanted pig hearts. Transplantation. 58: 330–7.PubMedGoogle Scholar
  189. Yu, P. B., Holzknecht, Z. E., Bruno, D., Parker, W., and Platt, J. L., 1996, Modulation of natural IgM binding and complement activation by natural IgG antibodies: a role for IgG anti-Gal α1–3Gal antibodies. J. Immunol. 157: 5163–8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Takaaki Kobayashi
    • 1
  • David K. C. Cooper
    • 2
  1. 1.Department of Surgery 11Nagoya University School of MedicineNagoyaJapan
  2. 2.Transplantation Biology Research CenterMassachusetts General Hospital/Harvard Medical SchoolBostonUSA

Personalised recommendations