Reduction of the Major Swine Xenoantigen, the α-Galactosyl Epitope by Transfection of the α2,3-Sialyltransferase Gene*

Reduction of the Major Swine Xenoantigen, the α-Galactosyl Epitope by Transfection of the α2,3-Sialyltransferase Gene*
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通过转染 α2,3-唾液酸转移酶基因减少主要猪异种抗原,即 α-半乳糖基表位*

DOI:
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发表时间:
1998
影响因子:
4.8
通讯作者:
N. Taniguchi
N. Taniguchi
中科院分区:
生物学2区
文献类型:
--
作者:
M. Tanemura;S. Miyagawa;S. Koyota;M. Koma;H. Matsuda;S. Tsuji;R. Shirakura;N. Taniguchi

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α2,3-唾液酸转移酶是一种假定的酶,可通过与 α1,3-半乳糖基转移酶在细胞内竞争共同受体底物来还原 Galα1-3Gal β1-4GlcNAc-R(α-半乳糖基表位)。本研究表明,α2,3-唾液酸转移酶基因的过表达可抑制猪内皮细胞对人天然抗体的抗原性,相对于对照细胞,抑制77%;相对于转染α1,2-岩藻糖基转移酶的细胞,抑制30%;此外,与对照细胞相比,补体介导的细胞裂解减少75%;与转染α1,2-岩藻糖基转移酶的细胞相比,补体介导的细胞裂解减少22%。 α1,2-岩藻糖基转移酶。还研究了α-半乳糖基表位被还原的机制。在使用α2,3-唾液酸转移酶的转染子中观察到α1,3-半乳糖基转移酶活性被抑制30-63%,并且α1,3-半乳糖基转移酶基因的mRNA表达也降低。数据表明,α2,3-唾液酸转移酶有效地减少了α-半乳糖基表位,其效果与α1,2-岩藻糖基转移酶一样好或更好,并且α-半乳糖基表位的减少不仅是由于底物竞争,而且是由于内源性α1,3-半乳糖基转移酶活性的总体降低。
α2,3-Sialyltransferase represents a putative enzyme that reduces the Galα1-3Gal β1-4GlcNAc-R (the α-galactosyl epitope) by intracellular competition with α1,3-galactosyltransferase for a common acceptor substrate. This study demonstrates that the overexpression of the α2,3-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 α1,2-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 α1,2-fucosyltransferase. The mechanism by which the α-galactosyl epitope was reduced was also studied. Suppression of α1,3-galactosyltransferase activity by 30–63% was observed in the transfectants with α2,3-sialyltransferase, and mRNA expression of the α1,3-galactosyltransferase gene was reduced as well. The data suggest that the α2,3-sialyltransferase effectively reduced the α-galactosyl epitope as well as or better than the α1,2-fucosyltransferase did and that the reduction of the α-galactosyl epitope is due not only to substrate competition but also to an overall reduction of endogenous α1,3-galactosyltransferase enzyme activity.
DOI: 10.1073/pnas.84.5.1369
发表时间: 1987-03-01
影响因子: 11.1
作者:
GALILI, U;CLARK, MR;MACHER, BA
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DOI: 10.4049/jimmunol.129.1.184
发表时间: 1982-07
影响因子: 4.4
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通讯作者: A. Nicholson‐Weller;J. Burge;D. Fearon;P. Weller;K. Austen
DOI: --
发表时间: 1989
期刊: The Journal of biological chemistry
影响因子: --
作者:
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DOI: 10.1016/0022-1759(83)90438-6
发表时间: 1983-01-01
影响因子: 2.2
作者:
KORZENIEWSKI, C;CALLEWAERT, DM
通讯作者: CALLEWAERT, DM
DOI: --
发表时间: 1992
期刊: The Journal of biological chemistry
影响因子: --
作者:
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通讯作者: Paulson,JC