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Modulation of αGal Epitope Expression on Porcine Cells

  • Mauro S. Sandrin
  • Ian F. C. McKenzie
Chapter
Part of the Subcellular Biochemistry book series (SCBI, volume 32)

Abstract

Xenotransplantation, the transplanting of organs from species other than humans, is now seen as a viable solution to the world wide problem of lack of supply of suitable human donors (Auchincloss, 1988; Auchincloss, 1990; Auchincloss and Sachs, 1998; Sachs, 1994). The major barrier to successful clinical xenotransplantation is the lack of an effective way of eliminating antibody and complement, which mediate hyperacute rejection involving natural human antibodies to Galα(l,3)Gal (αGal). Numerous studies have shown that the major, antigen to which all humans have naturally occurring antibodies, and therefore of importance when pig tissue is transplanted to humans, is the αGal carbohydrate epitope (Good et al., 1992; Sandrin et al., 1993; Cooper et al., 1994; Sandrin and McKenzie, 1994; McKenzie et al., 1994b; Sandrin et al., 1994b). The phenomenon of hyperacute graft rejection and the importance of αGal in the pig-to-primate xenograft hyperacute rejection has been reviewed elsewhere (Cooper et al; 1994; Sandrin and McKenzie; 1994; Sandrin et al., 1994b). Here we examine the importance of the αGal epitope in xenograft rejection; describe the α1,3galac-tosyltransferase enzyme (αGT) responsible for generating αGal, and describe transgenic strategies designed to eliminate or reduce expression of αGal, such that the epitope is no longer recognised by natural human antibodies or indeed by human NK cells, which have been recently reported to recognise αGal (Artrip et al., 1998; Inverardi et al., 1997).

Keywords

Hyperacute Rejection aGal Expression Porcine Cell Porcine Endothelial Cell aGal Antibody 
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.

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References

  1. Ariga, T., Yoshino, H., Ren, S., Pal, S., Katoh-Semba, R., and Yu, R. K., 1993, Activation of UOPgalactose: globotriaosylceramide α 1–3-galactosyltransferase during PC 120 cell differentiation induced by galactosylceramide. Biochemistry 31: 7904–7908.CrossRefGoogle Scholar
  2. Artrip, J. H., Kwiatkowski, P., Wang, S.-F., Tugulea, S., Ankersmit, J., Chisholm, L., Michler, R. E., McKenzie, I. F. C., Sandrin, M. S., and Itescu, S., 1998, Target cell susceptibility to lysis by human natural killer cells is augmented by α(1,3)-galactosyltransferase and reduced by α(1,2)fucosyltransferase.: (submitted).Google Scholar
  3. Arumugham, R. G., Hsieh, T. C., Tanzer, M. L., and Laine, R. A., 1986, Structures of the asparaginelinked sugar chains of laminin. Biochim. Biophys. Acta 883: 112–126.PubMedCrossRefGoogle Scholar
  4. Asano, M., Furukawa, K., Kido, M., Matsumoto, S., Umesaki, Y., Kochibe, N., and Iwakura, Y., 1997, Growth retardation and early death of β-1, 4-galactosyltransferase knockout mice with augmented proliferation andabnonnal differentiation ofepithelial cells. EMB0J. 16: 1850–1857.CrossRefGoogle Scholar
  5. Auchincloss, H., 1988, Xenogeneic transplantation. A review. Transplantation 46: 1–20.PubMedCrossRefGoogle Scholar
  6. Auchincloss, H., 1990, Xenografting: a review. Transplantation Reviews 4: 14–27.CrossRefGoogle Scholar
  7. Auchincloss, H. and Sachs, O. H., 1998, Xenogeneic transplantation. Annu. Rev. Immunol. 16: 433470.Google Scholar
  8. Baldmus, C. A., McKenzie, I. F. C., Winn, H. J., and Russell, P. S., 1973. Acute destruction by humoral antibody of rat skin grafted to mice. J. Immunol. 110: 1532–1541.Google Scholar
  9. Blanken, W. M. and Van den Eijnden, D. H., 1985. Biosynthesis oftenninal Galα1–3Galβ1–4GlcNAc oligosaccharide sequences on glycoconjugates. Purification and acceptor specificity ofa UDPGal: N-acetyllactosaminide α 1–3-galactosyltransferase from calf thymus. J. Biol. Chem. 260: 12927–12934.Google Scholar
  10. Borrebaeck, C. A. K., Malmborg, C., and Ohlin, M., 1993, Does endogenous glycosylation prevent the use ofmouse monoclonal antibodies as cancer therapeutics? Immunology Today 14: 477–479.PubMedCrossRefGoogle Scholar
  11. Groth, C. G., Korsgren, O., Wennberg, L., Tibell, A., Zhu, S., Sundberg, B., Soderlund, J., Biberfeld, P., Satake, M., Moller, E., Wallgren, A. C., and Karlsson-Parra, A., 1996, Xenoislet rejection following pig-to rat, pig-to-primate, and pig-to-man transplantation. Transplant. Proc. 28: 538–539.PubMedGoogle Scholar
  12. Haslam, D. B. and Baenziger, J. U., 1996, Expression cloning of Forssman glycolipid synthetase: a novel member of the histo-blood group ABO gene family. Proc. Natl. Acad. Sci. USA 93: 10697–10702.PubMedCrossRefGoogle Scholar
  13. Henion, T. R., Macher, B. A., Anaraki, F., and Galili, U., 1994, Defining the minimal size of catalyti-cally active primate α1,3galactosyltransferase: structure-function studies on the recombinant truncated enzyme. Glycobiology 4: 193–201.PubMedCrossRefGoogle Scholar
  14. Hoess, R., Brinkman, U., Handel, T., and Pastan, I., 1993, Identification of a peptide which binds to the carbohydrate-specific monoclonal antibody B3. Gene 128: 43–4Google Scholar
  15. Holzknecht, Z. E. and Platt, J. L., 1995, Identification of porcine endothelial cell membrane antigens recognized by human xenoreactive natural antibodies. J. Immunol. 154: 4565–4575.PubMedGoogle Scholar
  16. Inverardi, L., Clissi, B., Stolzer, A. L., Bender, J. R., Sandrin, M. S., and Pardi, R., 1997, Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 63: 1318–1330.PubMedCrossRefGoogle Scholar
  17. Ioffe, E. and Stanley, P., 1994, Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates. Proc. Natl. Acad. Sci. USA 91: 728–732.Google Scholar
  18. Joziasse, D. H., 1992, Mammalian glycosyltransferases: genomic organization and protein structure. Glycobiology 2: 271–277.Google Scholar
  19. Joziasse, D. H., Shaper, J. H., Jabs, E. W., and Sharper, N. L., 1991, Characterisation of an α1,3-galactosyltransferase homologue on human chromosome 12 that is organised as a processed pseudogene. J. Biol. Chem. 266: 6991–6998.PubMedGoogle Scholar
  20. Joziasse, D. H., Shaper, J. H., Van den Eijnden, D. H., Van den Tunen, A. J., and Sharper, N. L., 1989, Bovine α 1,3 galactosyltransferase: isolation and characterisation of a cDNA clone. Identification of homologous sequences in human genomic DNA. J. Biol. Chem. 264: 14290–14297.PubMedGoogle Scholar
  21. Joziasse, D. H., Shaper, N. L., Kim, D., Van den Eijnden, D. H., and Shaper, J. H., 1992, Murine α1,3 galactosyltransferase: A single gene locus specifies four isoforms of the enzyme by alternative spicing. J. Biol. Chem. 261: 5534–5541.Google Scholar
  22. Kelly, R. J., Ernst, L. K., Larsen, R. D., Bryant, J. G., Robinson, J. S., and Lowe, J. B., 1994, Molecular basis for H blood group deficiency in Bombay (Oh) and para-Bombay individuals. Proc Natl Acad Sci USA 91: 5843–5847.PubMedCrossRefGoogle Scholar
  23. Kelly, R. J., Rouquier, S., Giorgi, D., Lennon, G. G., and Lowe, J. B., 1995, Sequence and expression of a candidate for the human Secretor blood group α(l,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem 270: 4640–4649.PubMedCrossRefGoogle Scholar
  24. Koike, C., Kannagi, R., Takamura, Y., Akutsu, F., Hayashi, S., Hiraiwa, N., Kadomatsu, K., Muramatsu, T., Yamakawa, H., Nagui, T., Kobayshi, S., Okada, H., Nakashima, I., Uchida, K., Yokoyama, I., and Takagi, H., 1996, Introduction of α(,2)-fucosyltransferase and its effect on α-Gal epitopes in transgenic pig. Xenotransplantation 3: 81–86.CrossRefGoogle Scholar
  25. 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 the use in removing xenoreactive anit-αGal antibodies. Transplantation 61: 851–855.PubMedCrossRefGoogle Scholar
  26. Koulmanda, M., McKenzie, I. F. C., Sandrin, M. S., and Mandel, T. E., 1995, Fetal pig islet xenografts in NOD/Lt mice: The effects of peritransplant anti-CD4 monoclonal antibody and graft immunomodulation on graft survival, and lack of expression of Galα(1–3)GaI on endocrine cells. Xenotranplantation 2: 295–305.CrossRefGoogle Scholar
  27. Larsen, R. D., Emst, L. K., Nair, R. P., and Lowe, J. B., 1990a. Molecular cloning, sequence, and expression of a human GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferase cDNA that can form the H blood group antigen. Proc Natl Acad Sci USA 87: 6674–6678.PubMedCrossRefGoogle Scholar
  28. Larsen, R. D., Rajan, V. P., Ruff. M., Kukowskα-Latallo. J., Cummings, R. D., and Lowe. J. B., 1989. Isolation of a cDNA encoding a murine UDPgalactose:β-D-galctosyl-l,4-N-acetyl-glucosaminide-α-l,3-galactosyltransferase: Expression cloning by gene transfer. Proc. Natl. Acad. Sci. USA 86: 8227–8231.Google Scholar
  29. Larsen, R. D., Riverra-Marrero, C. A., Ernst, L. K., Cummings, R. D., and Lowe, J. B., 1990b, Frameshift and non sense mutations in a human genomic sequence homologous to a murine UDP-Gal:β-D-Gal 1,4-D-GlcNAcα1,3-galactosyl-transferase cDNA. J. Biol. Chem. 265: 7055–7061.PubMedGoogle Scholar
  30. Lu, Q., Hasty, P., and Shur, B. D., 1997. Targeted mutation in β 1,4-galactosyltransferase leads to pituitary insufficiency and neonatal lethality. Dev Biol. 181: 257–267.PubMedCrossRefGoogle Scholar
  31. Malyguine. A. M. Saadi. S., Platt. J. L., and Dawson. J. R., 1996. Human natural killer cells induce morphologic changes in porcine endothelial cell monolayers. Transplantation 61: 161–164.PubMedCrossRefGoogle Scholar
  32. McKenzie, I. F., Koulmanda, M., Mandel, T., Xing, P. X., and Sandrin, M. S., 1995a, Comparative studies of the major xenoantigen gal alpha( 1,3)gal in pigs and mice. Transplant Proc 27: 247–248.PubMedGoogle Scholar
  33. McKenzie, I. F., Xing, P. X., Vaughan. H. A., Prenzoska, J., Dabkowski, P. L., and Sandrin, M. S., 1994a, Distribution of the major xenoantigen (gal (α1–3)gal) for pig to human xenografts. Transpl. Immunol. 2: 81–86.PubMedCrossRefGoogle Scholar
  34. McKenzie, I. F. C., Koulmanda, M., Mandel, T. E., and Sandrin, M. S., 1995b. The expression of Galα(1–3)Gal by porcine islet cells and its relevance to xenotransplantation Xenotransplantalion 2: 139–142.CrossRefGoogle Scholar
  35. McKenzie. L. F. C. Koulmanda. M., Mandel. T. E., Xing. P.-X., and Sandrin. M. S., 1995c. Pig to human xenotransplantation: the expression of Galα(1–3)Gal epitopes on pig islet cells. Xenotransplantalion 2: 1–7.CrossRefGoogle Scholar
  36. McKenzie, I. F. C. Koulmanda, M., Mandell, T. E., and Sandrin, M. S., 1998a, Pig islet xenografts are susceptible to “anti-pig” but not to anti Galα(1.3)Gal antibody and complement in Gal o/o mice. J. Immunol.: (submitted).Google Scholar
  37. McKenzie, I. F. C., Li, Y. Q., Patton, K., Thall, A., and Sandrin, M. S., 1998b, A murine model for antibody mediated hyperacute rejection due to anti-Galα(l,3)Gal antibodies in Gal o/o mice. Transplantation: (in press).Google Scholar
  38. McKenzie, I. F. C., Osman, N., Cohney, S., Vaughan, H. A., Patton, K., Mouhtouris, E., Atkin, J., Elliot, E., Fodor, W. L., Squinto, S. P., Burton. D., Gallop, M. A., Oldenburg, K. R., and Sandrin, M. S., 1996, Strategies to overcome the anti-Galα( l,3)Gal reaction in xenotransplantation. Transplant. Proc. 28: 567.Google Scholar
  39. McKenzie, 1. F. C., Patton, K., Smit, J. A., Mouhtouris, E., Xing, P.-X., Myburgh, J. A., and Sandrin, M. S., 1998c, Definition and characterization of chicken Galα(l,3 )Gal antibodies. Transplantation: (in press).Google Scholar
  40. McKenzie, I. F. C., Vaughan, H. A., and Sandrin, M. S., 1994b, How important are anti-Galα(1–3)Gal antibodies in pig to human xenotransplants? Xeno 2: 107–110.Google Scholar
  41. Metzler, M., Gertz, A., Sarkar, M., Schachter, H., Schrader, J. W., and Marth, J. D., 1994, Complex asparagine-linked oligosaccharides are required for morphogenic events during postimplantation development. EMBOJ. 13: 2056–2065.Google Scholar
  42. Oldenburg, K. R., Loganathan. D., Goldstein, I. J., Schultz, P. G., and Gallop, M. A., 1992, Peptide lig-ands for a sugar-binding protein isolated from a random peptide library. Proc. Natl. Acad. Sci. USA 89: 5393–5397.PubMedCrossRefGoogle Scholar
  43. Oriol, R., Ye, Y., Koren, E., and Cooper, D. K., 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: 1433–1442.PubMedCrossRefGoogle Scholar
  44. Osman, N., McKenzie, I. F. C., Mouhtouris. E., and Sandrin, M. S., 1996, Switching amino terminal cytoplasmic domains of αl,2fucosyltransferase and α1,3galactosyltransferase alters the expression of H substance and Galα(l,3)Gal. J. Biol. Chem. 271: 33105–33109.PubMedCrossRefGoogle Scholar
  45. Osman, N., McKenzie, I. F. C., Ostenreid, K., Ioannou, Y. A., Desnick, R. J., and Sandrin, M. S., 1997, Combined transgenic expression of α-galactosidase and α1, 2fucosyltransferase leads to optimal reduction in the major xenoepitope Galα( l,3)Gal. Proc. Natl. Acad. Sci. USA 94: 14677–14682.PubMedCrossRefGoogle Scholar
  46. Petryniak, J., Varani, J., Ervin, P. R., and Goldstein, I. J., 1991, Differential expression of glycoproteins containing α-D-galactosyl groups on normal human breast epithelial cells and MCF-7 human breast carcinoma cells. Cancer Lett. 60: 59–65.PubMedCrossRefGoogle Scholar
  47. Platt, J. L. and Holznecht, Z. E., 1994, Porcine platelet antigens recognised by human xenoreactive natural antibodies. Transplantation 57: 327–335.PubMedCrossRefGoogle Scholar
  48. 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: 817–822.PubMedCrossRefGoogle Scholar
  49. Ryan, U. S., 1995, Complement inhibitory therapeutics and xenotransplantation. Nature Medicine 1: 967–968.PubMedCrossRefGoogle Scholar
  50. Sachs, D. H., 1994, The pig as a potential xenograft donor. Vetinary Immunology and Immunopathology 43: 185–191.CrossRefGoogle Scholar
  51. Sachs, D. H., Sykes, M., Greenstein, J. L., and Cosimi, A. B., 1995, Tolerance and xenograft survival. Nature Med. 1:969.Google Scholar
  52. 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: 151–168.PubMedCrossRefGoogle Scholar
  53. Sandrin, M. S. and McKenzie, I. F. C., 1994, Galα(l,3)Gal, the major xenoantigen(s) recognised in pigs by human natural antibodies. Immunol. Rev. 141: 169–190.PubMedCrossRefGoogle Scholar
  54. Sandrin, M. S., Cohney, S., Osman, N., and McKenzie, I. F. C: Overcoming the anti-Galα( 1,3)Gal rejection to avoid hyperacute reaction: molecular genetic approaches. In D. K. C. Cooper, E. Kemp, J. L. Platt, and D. J. G. White (eds.): Xenotransplantation: The transplantation of organs and tissues between species., pp. 683–700, Springer-Verlag, Berlin, 1997aGoogle Scholar
  55. Sandrin, M. S., Dabkowski, P. L., Henning, M. M., Mouhtouris, E., and McKenzie, I. F. C., 1994a, Characterization of cDNA clones for porcine α 1,3 galactosyltransferase: the enzyme generating the Galα(l,3)Gal epitope. Xenotransplantation 1: 81–88.CrossRefGoogle Scholar
  56. Sandrin, M.S., Fodor, W. L., Cohney, S., Mouhtouris. E., Osman, N., Rollins, S. A., Squinto, S. P., and McKenzie, I. F. C., 1996, Reduction of the major porcine xenoantigen Galot( 1,3)Gal by expression of α( 1,2)fucosyltransferase. Xenotransplantation 3; 134–140.CrossRefGoogle Scholar
  57. 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 remodeling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nature Medicine 1: 1261–1267.PubMedCrossRefGoogle Scholar
  58. Sandrin, M. S., Patton, K., and McKenzie, I. F. C., 1998, Inability to alter the rejection of Galα(l,3)Gal+ bone marrow by αl,2fucosyltransferase transgene. Transplantation (submitted).Google Scholar
  59. Sandrin, M. S., Vaughan, H. A., and McKenzie, I. F. C., 1994b, Identification of Galα(l,3)Gal as the major epitope for pig-to-human vascularised xenografts. Transplant. Rev. 8: 134–149.Google Scholar
  60. Sandrin, M.S., Vaughan, H. A., Dabkowski, P. L., and McKenzie, I. F. C., 1993, Anti-pig IgM antibodies in human serum reacts predominantly with Galα(l,3)Gal epitopes. Proc. Natl. Acad. Sci. USA 90: 11391–11395.PubMedCrossRefGoogle Scholar
  61. Sandrin, M. S., Vaughan, H. A., Xing, P.-X., and McKenzie, I. F. C. 1997b. Natural human antiGalα(l,3)Gal antibodies react with human mucin peptides. Glycoconjugate J. 14: 97–105.CrossRefGoogle Scholar
  62. Schaapherder, A. F. M., Dana. M. R., te Bulte. M.-J., van der Woude. F. J., and Gooszen. H. G., 1994. Anti-body-dependant cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera. Transplantation 57: 1376–1382.PubMedCrossRefGoogle Scholar
  63. Schnieke, A. E., Kind, A. J., Ritchie, W. A., Mycock, K., Scott, A. R., Ritchie, M., Wilmut. I., Colman, A., and Campbell, K. H., 1997, Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278: 2130–2133.PubMedCrossRefGoogle Scholar
  64. Scott, J. K., Loganathan, D., Easley, R. B., Gong, X., and Goldstein, I. J., 1992, A family of concanavalin A-binding peptides from a hexapeptide epitope library. Proc. Natl. Acad. Sci. USA 89: 5398–5402.PubMedCrossRefGoogle Scholar
  65. Shaper, N. L., Lin, S. P., Joziasse. D. H., Kim. D. Y., and Yang-Feng, T. L., 1992. Assignment of two human alpha-1,3-galactosyltransferase gene sequences (GGTA1 and GGTA1P) to chromosomes 9q33-q34 and 12ql4-ql5. Genomics 12: 613–615.PubMedCrossRefGoogle Scholar
  66. 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: 7190–7195.PubMedCrossRefGoogle Scholar
  67. Simon, P.M., Neethling, F. A., Taniguchi, S., Goode. P. L., Zopf, D., Hancock, W. W., and Cooper, D.K., 1998, Intravenous infusion of Galα1–3Gal oligosaccharides in baboons delays hyperacute rejection of porcine heart xenografts. Transplantation 65: 346–353.PubMedCrossRefGoogle Scholar
  68. Smith, D. F., Larsen. R. D., Mattox. S., Lowe, J. B., and Cummings. R. D., 1990. Transfer and expression of a murine UDP-Gal:β-D-Gal-α1,3-galactosyltransferase gene in transfected Chinese hamster ovary cells. Competition reactions between the α 1,3-galactosyltransferase and the endogenous α2,3-sialyltransferase. J. Biol. Chem. 265: 6225–6234.PubMedGoogle Scholar
  69. Strahan. K. M., Gu. F., Preece, A. F., Gustavsson. I., Andersson. L., and Gustafsson. K., 1995c DNA sequence and chromosome localization of pig alpha 1.3 galactosyltransferase. Immunogenelics 41: 101–105.Google Scholar
  70. Tanemura, M., Miyagawa. S., Ihara. Y., Mikata. S., Matsuda. H., Shirakura. R., and Taniguchi. N., 1997a, Reduction of the major swine xenoantigen Galα(1.3)Gal by transfection of N-acetylglucosaminyltransferase III (GnT-III) gene. Transplant. Proc. 29: 891–892.PubMedCrossRefGoogle Scholar
  71. Tanemura. M., Miyagawa, S., Ihara. Y., Nishikawa. A., Suzuki. M., Yamamura, K., Matsuda. H., Shirakura. R., and Taniguchi, N., 1997b. Suppression of the xenoantigen Galα(l,3)Gal by N-acetylglucosaminyltransferase III (GnT-III) in transgenic mice. Transplant. Proc. 29: 895–896.PubMedCrossRefGoogle Scholar
  72. Tanemura, M., Miyagawa, S., Ihara. Y., Matsuda. H., Tsuji. S., Shirakura, R., and Taniguchi, N., 1997a. Coexpression of N-acetylglucosaminyltransferase III (GnTIII) and α2,3sialyl-transferase (α2,3ST) gene for reduction of xenoantigens.: (in press).Google Scholar
  73. Tanemura, M., Miyagawa, S., Ihara, Y., Matsuda, H., Tsuji, S., Shirakura, R., and Taniguchi, N., 1997b, Effects of Galβl,4GlcNAc3-α-D-sialyltransferase on reduction of the swine xenoantigen. (in press).Google Scholar
  74. Tearle, R. G., Tange, M. J., Zannettino, Z. L., Katerelos. M., Shinkel. T. A., Van Denderen, B. J. W., 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. F., 1996, The α-1,3-galactosyltransferase knockout mouse: implications for xenotransplantation. Transplantation 61: 13–19.PubMedCrossRefGoogle Scholar
  75. Thall, A. and Galili, U., 1990, Distribution of Galα 1–l→3Galβl →4GlcNAc residues on secreted mammalian glycoproteins (thyroglobulin, fibrinogen, and immunoglobulin G) as measured by a sensitive solid-phase radioimmunoassay. Biochemistry 29: 3959–3965.PubMedCrossRefGoogle Scholar
  76. Thall, A. D., Maly, P., and Lowe, J. B., 1995, Oocyte Galα1,3Gal Epitopes implicated in sperm adhesion to the zona pellucida glycoprotein ZP3 are not required for fertilization in the mouse. J. Biol. Chem. 270: 21437–21440.PubMedCrossRefGoogle Scholar
  77. Vaughan, H. A., McKenzie, I. F. C., and Sandrin, M. S., 1995a, Biochemical studies of pig xenoantigens detected by naturally occurring human antibodies and the galactoseα(1–3)galactose reactive lectin. Transplantation 59: 102–109.PubMedCrossRefGoogle Scholar
  78. Vaughan, H. A., Oldenburg, K. R., Gallop, M. A., Atkin, J. D., McKenzie, I. F. C., and MS., S., 1995b, Recognition of an octapeptide sequence by multiple Galα(l,3)Gal-binding proteins. Xenotransplantation 3: 18–23.CrossRefGoogle Scholar
  79. Waiter, H., Gullaumin, J. M., Vallee, I., Thibault, G., Gruel, Y., Leraunchu, Y., and Bardos, P., 1996, Human NK cell-mediated direct and IgG-dependent cytotoxicity against xenogeneic porcine endothelial cells. Transplant. Immunol. 4: 293–299.CrossRefGoogle Scholar
  80. Welsh, R. M., O’Donnell, C. L., Reed, D. J., and Rother, R. P., 1998, Evaluation of the Galα1–3Gal epitope as a host modification factor eliciting natural humoral immunity to enveloped viruses. J. Virol. 72: 4650–4656.PubMedGoogle Scholar
  81. Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J., and Campbell, K. H. S., 1997, Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810–813.PubMedCrossRefGoogle Scholar
  82. Winn, H. J., Baldmus, C. A., Jooste, S. V., and Russell, P. S., 1973, Acute destruction by humoral antibody of rat skin grafted to mice: The role of complement and polymorphonuclear granulocytes. J. Exp. Med. 137:893–910.PubMedCrossRefGoogle Scholar
  83. Xu, Y., Lorf, T., Sablinski, T., Gianello, P., Bailin, M., Monroy, R., Kozlowski, T., Awwad, M., Cooper, D. K., and Sachs, D. H., 1998, Removal of anti-porcine natural antibodies from human and nonhuman primate plasma in vitro and in vivo by a Galα1-3Galβ1–4βGlc-X immunoaffinity column. Transplantation 65: 172–179.PubMedCrossRefGoogle Scholar
  84. Yamamoto, F., Clausen, H., White, T., Marken, J., and Hakmori, S., 1990, Molecular genetic basis of the histo-blood group ABO system. Nature 345: 229–233.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Mauro S. Sandrin
    • 1
  • Ian F. C. McKenzie
    • 1
  1. 1.Molecular lmmunogenetics Laboratory, Austin Research InstituteAustin and Repatriation Medical CentreHeidelbergAustralia

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