A comparison of the main structures of N-glycans of porcine islets with those from humans

A comparison of the main structures of N-glycans of porcine islets with those from humans
复制标题

猪胰岛与人类胰岛 N-聚糖主要结构的比较

DOI:
10.1093/glycob/cwt088
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发表时间:
2014
期刊:
影响因子:
4.3
通讯作者:
Nagashima H
Nagashima H
中科院分区:
生物学3区
文献类型:
--
作者:
Miyagawa S;Maeda A;Kawamura T;Ueno T;Usui N;Kondo S;Matsumoto S;Okitsu T;Got o M;Nagashima H

文献摘要

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生产α1-3-半乳糖基转移酶敲除(GKO)猪后,这些猪的大部分器官对人体的抗原性降低。然而,最初含有可忽略水平的α-半乳糖苷酶的野生型成年猪胰岛(API)现在显示出对人血清的明确抗原性。在本研究中,从API和人胰岛中分离N-聚糖。它们的结构进行了分析,然后通过映射技术的基础上,其高效液相色谱洗脱位置和基质辅助激光解吸/电离飞行时间质谱数据。两种制剂均含有大量高甘露糖结构。从人胰岛中分离出17个中性、8个单唾液酸和4个二唾液酸聚糖,其中API聚糖由11个中性、8个单唾液酸、3个二唾液酸、2个单硫酸化、3个单唾液酸单硫酸化和1个二硫酸化聚糖组成。其中,API制剂含有1种中性聚糖、5种单唾液酸聚糖和6种硫酸化聚糖,在人胰岛中未检出。这12个中的9个的结构可以清楚地确定。此外,对硫酸盐耗尽的API的研究表明,硫酸盐残留物可能对人类具有抗原性。本文的数据将有助于进一步研究与API相关的抗原性。
After producing α1-3-galactosyltransferase knockout (GKO) pigs, most of the organs of these pigs showed less antigenicity to the human body. However, wild-type adult pig islets (API) that originally contained negligible levels of α-galactosidase now showed a clear antigenicity to human serum. In this study,N-glycans were isolated from both APIs and human islets. Their structures were then analyzed by a mapping technique based on their high-performance liquid chromatography elution positions and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometric data. Both preparations contained substantial amounts of high-mannose structures. TheN-glycans from human islets were separated into 17 neutral, 8 mono-sialyl and 4 di-sialyl glycans, and the API glycans were comprised of 11 neutral, 8 mono-sialyl, 3 di-sialyl, 2 mono-sulfated, 3 mono-sialyl-mono-sulfated and 1 di-sulfated glycans. Among them, the API preparation contained one neutral, five mono-sialyl glycans and six sulfated glycans that were not detected in human islets. The structures of 9 of these 12 could be clearly determined. In addition, a study of the sulfate-depleted API suggests that sulfate residues could be antigenic to humans. The data herein will be helpful for future studies of the antigenicity associated with API.