Reduction of the major swine xenoantigen, the alpha-galactosyl epitope by transfection of the alpha2,3-sialyltransferase gene.

The Journal of Biological Chemistry
M TanemuraN Taniguchi

Abstract

alpha2,3-Sialyltransferase represents a putative enzyme that reduces the Galalpha1-3Gal beta1-4GlcNAc-R (the alpha-galactosyl epitope) by intracellular competition with alpha1,3-galactosyltransferase for a common acceptor substrate. This study demonstrates that the overexpression of the alpha2,3-sialyltransferase gene suppresses the antigenicity of swine endothelial cells to human natural antibodies by 77% relative to control cells and by 30% relative to cells transfected with alpha1,2-fucosyltransferase, and in addition, it reduces the complement-mediated cell lysis by 75% compared with control cells and by 22% compared with cells transfected with alpha1, 2-fucosyltransferase. The mechanism by which the alpha-galactosyl epitope was reduced was also studied. Suppression of alpha1, 3-galactosyltransferase activity by 30-63% was observed in the transfectants with alpha2,3-sialyltransferase, and mRNA expression of the alpha1,3-galactosyltransferase gene was reduced as well. The data suggest that the alpha2,3-sialyltransferase effectively reduced the alpha-galactosyl epitope as well as or better than the alpha1, 2-fucosyltransferase did and that the reduction of the alpha-galactosyl epitope is due not only to substrate competition ...Continue Reading

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Citations

Mar 14, 2002·Journal of Neuroscience Research·Thia BabovalFrances I Smith
Aug 11, 2000·Transplantation Proceedings·M KomaN Taniguchi
Dec 20, 2000·Transplantation Proceedings·M KomaN Taniguchi
Oct 6, 1999·Current Opinion in Immunology·M S Sandrin, I F McKenzie
Apr 2, 2002·Journal of Cardiac Surgery·M S SandrinI F McKenzie
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Jun 10, 2005·Xenotransplantation·Mohamed Ezzelarab, David K C Cooper
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