Control of macrophage function through modulating carbohydrate structute of immunoglobulin G.

通过调节免疫球蛋白 G 的碳水化合物结构来控制巨噬细胞功能。

• 批准号: 14572186
• 负责人: KIMURA Satoshi
• 金额: $ 1.98万
• 依托单位: Showa University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14572186/
• 关键词: IgG; carbohydrate structure; chronic ischemia; ischemia modified albumin; ischemia modified albumin; 子宮内発育遅延; Ischemia Modified Albumin; マクロファージ; 胎盤機能; carbohydrate; allergy

N-linked oligosaccharides in human IgG are known to modulate immunological function. Complex oligosaccharide moieties (biantennary mannose structure, with or without galactose on N-acetylglucosamine outer arms) are attached to asparagine-297 of gamma heavy chains. We previously showed that neonatal cord blood IgG has significantly higher ratio of galactose on its outer arms, compared to that of normal healthy adults [Kimura S, et al. ; Clin Chim Acta. 2000; 299:169-77]. Because the galactose-rich IgGs are supplied from maternal sera, it is possible that the carbohydrate structure could affect the efficacy of IgG transportation via placenta. Based on this idea, we characterized, carbohydrate structures on neonatal serum IgG; to compare with their mothers' sera.Cord blood samples (n=12; five males and seven females including twins) were collected during deliveries at Dokkyo University Koshigaya Hospital, with the parents' written consent. Their mothers' blood samples (n =11, age 31.3±3.9 … More ) were also collected within a week before delivery The analysis of carbohydrate structure was performed as previously described by us. Briefly, IgG was isolated using a protein A-conjugated Sepharose CL-4B column, followed by neuraminidase digestion. Oligosaccharyl amines were released by rN-glycanase treatment from reduced, carboxymethylated IgG proteins. They were labeled with 9-Fluorenylmethyl chloride, analyzed with HPLC using TSK- GEL Amide 80 column.Concentration of G2 and G1-IgG were siginificantly higher than that of GO in both neonates and thier mothers (P<0.001, in all cases). Concentration of G2 was significantly higher than that of G1 in both neonates and mothers (p<0.001). Between mothers and neonates, there was no significant difference in total, GO, G1 or G2 concentrations. There was no significant difference of %GO (percent of GO IgG in total IgG), %G1, %G2 between mothers and neonates, either. There were no significant differences of G1/GO and G2/G0 ratio between mothers and neonates (p=0.268, p=0.285, respectively). There was a strong correlation of GO concentration between mothers and neonates (r=0.9355), however, there were weak or no correlation of G2 (r=0.3982) and G1 (r=0.1311) concentration. Concentration of GO, G1, G2 in twins (case 5 and 6) showed almost similar results.In conclusion, Concentration of galactosyl IgG was significantly increased than that of agalactosyl IgG, in both mothers and neonates. There was no significant difference in total, GO, G1 or G2-IgG concentrations between mothers and neonates. Less

已知人IgG中的N-连接寡糖调节免疫功能。复合寡糖部分（双触角甘露糖结构，在N-乙酰葡糖胺外臂上有或没有半乳糖）与γ重链的天冬酰胺-297连接。我们先前表明，与正常健康成人相比，新生儿脐带血IgG在其外臂上具有显著更高的半乳糖比率[Kimura S等人; Clin Chim Acta. 2000; 299：169-77]。由于富含半乳糖的IgG由母体血清提供，因此碳水化合物结构可能会影响IgG通过胎盘转运的功效。基于这一想法，我们表征了新生儿血清IgG上的碳水化合物结构，以与他们的母亲血清进行比较。脐带血样本（n=12; 5名男性和7名女性，包括双胞胎）是在Dokkyo大学越谷医院分娩时收集的，并得到父母的书面同意。11例（31.3±3.9 ...更多信息 ）也在分娩前一周内收集。碳水化合物结构的分析如我们先前所述进行。简言之，使用蛋白A缀合的Sepharose CL-4 B柱分离IgG，然后进行神经氨酸酶消化。寡糖胺通过rN-聚糖酶处理从还原的羧甲基化IgG蛋白中释放。用9-芴基甲基氯标记，用TSK-GEL Amide 80柱进行HPLC分析，结果表明，新生儿及其母亲血清中G2和G1-IgG浓度均显著高于GO（P<0.001）。新生儿和母亲的G2浓度均显著高于G1（p<0.001）。在母亲和新生儿之间，总浓度、GO、G1或G2浓度无显著差异。母亲与新生儿的%GO（GO IgG占总IgG的百分比）、%G1、%G2差异无统计学意义。G1/GO和G2/G 0比值在母亲和新生儿之间无显著差异（分别为p=0.268和p=0.285）。母亲与新生儿的GO浓度有较强的相关性（r=0.9355），而G2（r=0.3982）和G1（r=0.1311）浓度则无相关性或弱相关性。双胞胎（例5和例6）的GO、G1、G2浓度几乎相同，说明母亲和新生儿的半乳糖基IgG浓度均显著高于无半乳糖基IgG。母亲和新生儿之间的总、GO、G1或G2-IgG浓度无显著差异。少

项目成果

Ischemia-modified albumin levels in cord blood : A case control study in uncomplicated and complicated deliveries.

脐带血中缺血修饰的白蛋白水平：简单和复杂分娩的病例对照研究。

• 发表时间: 2005
• 期刊: Clinica Chimica Acta 362
• 作者: Alejandro Gugliucci;Ricardo Hermo;Carolina Monroy;Masahide Numaguchi;Satoshi Kimura
• 通讯作者: Satoshi Kimura