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Titolo:
Xenotransplantation: in vitro analysis of synthetic alpha-galactosyl inhibitors of human anti-Gal alpha 1 -> 3Gal IgM and IgG antibodies
Autore:
Rieben, R; Bovin, NV; Korchagina, EY; Oriol, R; Nifantev, NE; Tsvetkov, DE; Daha, MR; Mohacsi, PJ; Joziasse, DH;
Indirizzi:
Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland Univ Hosp Bern Bern Switzerland CH-3010 rdiol, CH-3010 Bern, Switzerland Russian Acad Sci, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117871, Russia Russian Acad Sci Moscow Russia 117871 oorgan Chem, Moscow 117871, Russia INSERM, U504, F-94807 Villejuif, France INSERM Villejuif France F-94807INSERM, U504, F-94807 Villejuif, France Univ Paris S 11, F-94807 Villejuif, France Univ Paris S 11 Villejuif France F-94807 S 11, F-94807 Villejuif, France Russian Acad Sci, ND Zelinskii Organ Chem Inst, Moscow 117913, Russia Russian Acad Sci Moscow Russia 117913 n Chem Inst, Moscow 117913, Russia Leiden Univ, Med Ctr, Dept Nephrol, NL-2300 RC Leiden, Netherlands Leiden Univ Leiden Netherlands NL-2300 RC NL-2300 RC Leiden, Netherlands Free Univ Amsterdam, Dept Med Chem, NL-1081 BT Amsterdam, Netherlands FreeUniv Amsterdam Amsterdam Netherlands NL-1081 BT terdam, Netherlands
Titolo Testata:
GLYCOBIOLOGY
fascicolo: 2, volume: 10, anno: 2000,
pagine: 141 - 148
SICI:
0959-6658(200002)10:2<141:XIVAOS>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYPERACUTE XENOGRAFT REJECTION; EPITOPE-MEDIATED ACTIVATION; AORTIC ENDOTHELIAL-CELLS; HUMAN NATURAL ANTIBODIES; ACCEPTOR SPECIFICITY; CARDIAC XENOGRAFTS; TRANSGENIC MICE; IN-VIVO; OLIGOSACCHARIDES; PIG;
Keywords:
xenotransplantation; xenoreactive antibodies; oligosaccharides; glycoconjugates; chemico-enzymatic synthesis; alpha 1 -> 3-galactosyltransferase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Rieben, R Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland Univ Hosp Bern Bern Switzerland CH-3010 3010 Bern, Switzerland
Citazione:
R. Rieben et al., "Xenotransplantation: in vitro analysis of synthetic alpha-galactosyl inhibitors of human anti-Gal alpha 1 -> 3Gal IgM and IgG antibodies", GLYCOBIOLOG, 10(2), 2000, pp. 141-148

Abstract

Pig-to-human xenotransplantation might be an option to overcome the increasing shortage of human donor organs. However, naturally occurring antibodies in human blood against the Gal alpha 1-->3Gal antigen on pig endothelial cells lead to hyperacute or, if prevented, acute or delayed vascular rejection of the pig graft. The purpose of this study was therefore to evaluate synthetic oligosaccharides with terminal Gal alpha 1-->3Gal to inhibit antigen-binding and cytotoxicity of anti-alpha Gal antibodies against pig cells. Different oligosaccharides were synthesized chemically and by a combined chemico-enzymatic approach. These included monomeric di-, tri, and pentasaccharides, a polyacrylamide-conjugate (PAA-Bdi), as well as di-, tetra-, and octamers of Gal alpha 1-->3Gal. All were tested for inhibitory activity by anti-alpha Gal ELISA and complement-dependent cytotoxicity tests. PAA-Bdi was the best inhibitor of binding as well as cytotoxicity of anti-alpha Gal antibodies. Monomeric oligosaccharides efficiently prevented binding of anti-alpha Gal IgG, but less well that of anti-alpha Gal IgM, with tri- and pentasaccharides showing a better efficacy than the disaccharide. The two trisaccharides Gal alpha 1-->3Gal beta 1-->4GlcNAc and Gal alpha 1-->3Gal beta1-->3GlcNAc were equally effective. Oligomers of Gal alpha 1-->3Gal were more effective than monomers in blocking the binding of anti-alpha Gal IgG, However, they could not block IgM binding, nor could they match the efficacy of PAA-Bdi, We conclude that oligosaccharides with terminal Gal alpha 1-->3Gal, most effectively as PAA-conjugates, can prevent binding and cytotoxicity of human anti-alpha Gal in vitro. The PAA-Bdi conjugate might be most suited for use as a Sepharose-bound immunoabsorption material.

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Documento generato il 11/07/20 alle ore 21:13:55