The impact of the α1,3-galactosyltransferase gene knockout pig on xenotransplantation

Current Opinion in Organ Transplantation

Volumn 12, Issue 2, 2007, Pages 154-157

  Sandrin, Mauro S ^a   Milland, Julie ^a   Christiansen, Dale ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Acute vascular rejection; Carbohydrate; iGb3; Knockout pigs

Indexed keywords

ALPHA 1,3 GALACTOSYLTRANSFERASE; CARBOHYDRATE; CD161 ANTIGEN; EPITOPE; GALACTOSYLGALACTOSE; IGB3 SYNTHASE; INTERLEUKIN 4; LACTOSE; N ACETYLLACTOSAMINE; SYNTHETASE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ACUTE VASCULAR REJECTION; BLOOD CLOTTING; CARBOHYDRATE ANALYSIS; ENDOTHELIUM CELL; ENZYME SYNTHESIS; GRAFT REJECTION; GRAFT SURVIVAL; HUMAN; HYPERACUTE GRAFT REJECTION; KNOCKOUT GENE; MICROANGIOPATHY; NATURAL KILLER CELL; NONHUMAN; REVIEW; SWINE; XENOTRANSPLANTATION;

EID: 34250646610     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0b013e328028fdd8     Document Type: Review

References (38)

1. Sandrin MS, Loveland BE, McKenzie IF. Genetic engineering for xenotransplantation. J Card Surg 2001; 16:448-457.
2. Sandrin MS, Fodor WL, Mouhtouris E, et al. Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nat Med 1995; 1:1261-1267.
3. Dai Y, Vaught TD, Boone J, et al. Targeted disruption of the α1,3-galactosyltransferase gene in cloned pigs. Nat Biotechnol 2002; 20:251-255.
4. Lai L, Kolber-Simonds D, Park KW, et al. Production of α-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 2002; 295:1089-1092.
5. Phelps CJ, Koike C, Vaught TD, et al. Production of α1,3-galactosyltransferase-deficient pigs. Science 2003; 299:411-414.
6. Sandrin MS, McKenzie IF. Galα(1,3)Gal, the major xenoantigen(s) recognised in pigs by human natural antibodies. Immunol Rev 1994; 141:169-190.
7. Loveland BE, Milland J, Kyriakou P, et al. Characterization of a CD46 transgenic pig and protection of transgenic kidneys against hyperacute rejection in nonimmunosuppressed baboons. Xenotransplantation 2004; 11:171-183.
8. Bhatti FN, Schmoeckel M, Zaidi A, et al. Three-month survival of HDAF transgenic pig hearts transplanted into primates. Transplant Proc 1999; 31:958.
9. Kuwaki K, Knosalla C, Dor FJ, et al. Suppression of natural and elicited antibodies in pig-to-baboon heart transplantation using a human antihuman CD154 mAb-based regimen. Am J Transplant 2004; 4:363-372.
10. -/- pig organs to primates using various immunosuppression.
11. -/- pig organs to primates using various immunosuppression.
12. -/- pig organs to primates using various immunosuppression.
13. Dorling A. Are antiendothelial cell antibodies a prerequisite for the acute vascular rejection of xenografts? Xenotransplantation 2003; 10:16-23.
14. Schuurman HJ, Cheng J, Lam T. Pathology of xenograft rejection: a commentary. Xenotransplantation 2003; 10:293-299.
15. Gollackner B, Goh SK, Qawi I, et al. Acute vascular rejection of xenografts: roles of natural and elicited xenoreactive antibodies in activation of vascular endothelial cells and induction of procoagulant activity. Transplantation 2004; 77:1735-1741.
16. Ierino FL, Kozlowski T, Siegel JB, et al. Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts. Transplantation 1998; 66:1439-1450.
17. Crikis S, Cowan PJ, D'Apice AJ. Intravascular Thrombosis in Discordant Xenotransplantation. Transplantation 2006; 82:1119-1123. This paper reviews the problems of thrombotic problems observed in xenotransplantation and potential strategies to overcome these.
18. Milland J, Christiansen D, Lazarus BD, et al. The molecular basis for Galα(1,3)Gal expression in animals with a deletion of the α1,3galactosyltransferase gene. J Immunol 2006; 176:2448-2454. This paper describes the isolation of mouse cDNA for iGb3S and describes the presence of mRNA in pigs.
19. Sharma A, Naziruddin B, Cui C, et al. Pig cells that lack the gene for α1-3galactosyltransferase express low levels of the Gal antigen. Transplantation 2003; 75:430-436.
20. Keusch JJ, Manzella SM, Nyame KA, et al. Expression cloning of a new member of the ABO blood group glycosyltransferases, iGb3 synthase, that directs the synthesis of isoglobo-glycosphingolipids. J Biol Chem 2000; 275:25308-25314.
21. Taylor SG, McKenzie IF, Sandrin MS. Characterization of the rat α(1,3)galactosyltransferase: evidence for two independent genes encoding glycosyltransferases that synthesize Galα(1, 3)Gal by two separate glycosylation pathways. Glycobiology 2003; 13:327-337.
22. Kojima Y, Fukumoto S, Furukawa K, et al. Molecular cloning of globotriaosylceramide/ CD77 synthase, a glycosyltransferase that initiates the synthesis of globo series glycosphingolipids. J Biol Chem 2000; 275:15152-15156.
23. Xia C, Yao Q, Schumann J, et al. Synthesis and biological evaluation of α-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3). Bioorg Med Chem Lett 2006; 16:2195-2199.
24. -/- animals.
25. Milland J, Christiansen D, Sandrin MS. α1,3-galactosyltransferase knockout pigs are available for xenotransplantation: are glycosyltransferases still relevant? Immunol Cell Biol 2005; 83:687-693.
26. Shinkel TA, Chen CG, Salvaris E, et al. Changes in cell surface glycosylation in α1,3-galactosyltransferase knockout and alpha1,2-fucosyltransferase transgenic mice. Transplantation 1997; 64:197-204.
27. Ezzelarab M, Hara H, Busch J, et al. Antibodies directed to pig non-Gal antigens in naive and sensitized baboons. Xenotransplantation 2006; 13:400-407.
28. Hara H, Ezzelarab M, Rood PP, et al. Allosensitized humans are at no greater risk of humoral rejection of GT-KO pig organs than other humans. Xenotransplantation 2006; 13:357-365. This paper shows that serum from sensitized individuals would not have a higher risk of rejecting pig organs than nonsensitized individuals.
29. Goodman DJ, Von Albertini M, Willson A, et al. Direct activation of porcine endothelial cells by human natural killer cells. Transplantation 1996; 61:763-771.
30. Itescu S, Kwiatkowski P, Artrip JH, et al. Role of natural killer cells, macrophages, and accessory molecule interactions in the rejection of pig-to-primate xenografts beyond the hyperacute period. Hum Immunol 1998; 59:275-286.
31. Dawson JR, Vidal AC, Malyguine AM. Natural killer cell-endothelial cell interactions in xenotransplantation. Immunol Res 2000; 22:165-176.
32. Artrip JH, Kwiatkowski P, Michler RE, et al. Target cell susceptibility to lysis by human natural killer cells is augmented by α(1,3)-galactosyltransferase and reduced by α(1,2)- fucosyltransferase. J Biol Chem 1999; 274:10717-10722.
33. Costa C, Barber DF, Fodor WL. Human NK cell-mediated cytotoxicity triggered by CD86 and Galα(1,3)Gal is inhibited in genetically modified porcine cells. J Immunol 2002; 168:3808-3816.
34. Inverardi L, Clissi B, Stolzer AL, et al. Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues. Transplantation 1997; 63:1318-1330.
35. Miyagawa S, Nakai R, Yamada M, et al. Regulation of natural killer cell-mediated swine endothelial cell lysis through genetic remodeling of a glycoantigen. J Biochem (Tokyo) 1999; 126:1067-1073.
36. Baumann BC, Forte P, Hawley RJ, et al. Lack of galactose-alpha-1,3-galactose expression on porcine endothelial cells prevents complement-induced lysis but not direct xenogeneic NK cytotoxicity. J Immunol 2004; 172:6460-6467.
37. Baumann BC, Schneider MK, Lilienfeld BG, et al. Endothelial cells derived from pigs lacking Galα(1,3)Gal: no reduction of human leukocyte adhesion and natural killer cell cytotoxicity. Transplantation 2005; 79:1067-1072.
38. He Z, Ehrnfelt C, Kumagai-Braesch M, et al. Aberrant expression of alpha-Gal on primary human endothelium does not confer susceptibility to NK cell cytotoxicity or increased NK cell adhesion. Eur J Immunol 2004; 34:1185-1195.