Reduction of the Gal-alpha1,3-Gal epitope of mouse endothelial cells by transfection with the N-acetylglucosaminyltransferase III gene.
In order to prevent hyperacute rejection in pig-to-human xenotransplantation, it would be very useful to be able to down-regulate the Gal alpha1-3 Galbeta 1-4 GlcNAc-R (alpha-Gal epitope) in mouse and swine tissues. When the beta-D-mannoside beta-1,4-N-acetylglucosaminyl-transferase III (GnT-III) gene was introduced into mouse aorta endothelial cells (MEC) their susceptibility to complement-mediated cell lysis by normal human serum (NHS) was reduced. Expression of GnT-III also suppressed the antigenicity of MEC to human natural antibodies as shown by binding of Griffonia simplicifolia 1 isolectin (GS1B4 lectin) to the alpha-Gal epitope. Western blot analysis indicated that the reactivity of the glycoproteins of the transfectants to NHS and GSIB4 lectin was reduced to approximately the same extent. Thus GnT-III, a key enzyme involved in the formation of branched N-linked sugars, reduces the expression of xenoantigens, suggesting that this approach may be of value in clinical xenotransplantation.
Chung
Tae-Wook
TW
National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Department of Biochemistry and Molecular Biology, Dongguk University College of Oriental Medicine, Kyungju 780-714, Korea.
Kim
Kyoung-Sook
KS
Kim
Cheorl-Ho
CH
D000818:Animals; D004187:Disaccharides / Q000378:metabolism*; D042783:Endothelial Cells / Q000201:enzymology; D000939:Epitopes; D051379:Mice; D008822:Mice, Transgenic; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D004187:Disaccharides; D000939:Epitopes; C055075:galactosyl-(1-3)galactose; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase