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比较糖化卵清蛋白单糖在 BALB/c 小鼠模型中对卵清蛋白诱导的过敏反应的抑制作用。

Comparison of Glycated Ovalbumin-Monosaccharides in the Attenuation of Ovalbumin-Induced Allergic Response in a BALB/C Mouse Model.

机构信息

Department of Food Science , University of Guelph , 50 Stone Road East , Guelph , Ontario N1G 2W1 , Canada.

出版信息

J Agric Food Chem. 2019 Jul 24;67(29):8138-8148. doi: 10.1021/acs.jafc.9b02132. Epub 2019 Jul 11.

DOI:10.1021/acs.jafc.9b02132
PMID:31294563
Abstract

The aim of the present study was to compare various glycated ovalbumin (OVA)-monosaccharides, including OVA-mannose (Man), -glucose, -ribose, and -fructose, in the attenuation of OVA-induced allergic response in a BALB/C mouse model and the potential mechanisms of immunological modulation. The glycated OVA forms were prepared by Maillard reactions. OVA-Man significantly reduced the frequency of allergic signs. Mouse mast cell protease enzyme concentration was significantly reduced in the OVA-Man group (549.80 ± 84.67 ng/mL, < 0.05). The OVA-Man group also had a lower histamine concentration (30.96 ± 1.12 ng/mL) as compared with the positive control OVA group (44.43 ± 0.71 ng/mL, < 0.05). Both specific IgG and IgE were significantly reduced in the OVA-Man-treated group ( < 0.05). The OVA-Man group exhibited decreased concentrations of IL-4 (67.98 ± 3.11 pg/mL) and IL-17 (67.98 ± 3.11 pg/mL) and an increased concentration of IL-12 (336.70 ± 18.69 pg/mL, < 0.05) compared with the positive control. Mannosylation played a vital role in allergen recognition, implicating deleterious downstream Th2 cell activation, cytokine secretion, and IgE production. This result indicates that different glycans target specific DC receptors, and differential DC processing, antigen presentation, and T cell response leads to altered variation in allergic response. OVA-Man exhibited minimal DC internalization, DC processing, MHC antigen presentation, and antigen-specific T cell activation, resulting in an attenuated allergic response and validating its efficacy as a potential immunotherapeutic candidate to treat egg allergy.

摘要

本研究旨在比较不同糖基化卵清蛋白(OVA)单糖,包括 OVA-甘露糖(Man)、-葡萄糖、-核糖和 -果糖,在 BALB/C 小鼠模型中对 OVA 诱导的过敏反应的抑制作用及潜在的免疫调节机制。糖基化 OVA 形式通过美拉德反应制备。OVA-Man 可显著降低过敏症状的频率。OVA-Man 组小鼠肥大细胞蛋白酶浓度明显降低(549.80±84.67ng/ml,<0.05)。与阳性对照 OVA 组(44.43±0.71ng/ml,<0.05)相比,OVA-Man 组组胺浓度也较低。OVA-Man 治疗组特异性 IgG 和 IgE 均明显降低(<0.05)。与阳性对照组相比,OVA-Man 组 IL-4(67.98±3.11pg/ml)和 IL-17(67.98±3.11pg/ml)浓度降低,IL-12(336.70±18.69pg/ml)浓度升高(<0.05)。甘露糖化在变应原识别中起关键作用,暗示有害的下游 Th2 细胞激活、细胞因子分泌和 IgE 产生。这一结果表明,不同的聚糖靶向特定的 DC 受体,而 DC 的不同处理、抗原呈递和 T 细胞反应导致过敏反应的变化。OVA-Man 表现出最小的 DC 内化、DC 处理、MHC 抗原呈递和抗原特异性 T 细胞激活,导致过敏反应减弱,验证了其作为治疗鸡蛋过敏的潜在免疫治疗候选物的功效。

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