A novel strategy for the generation of anti-glycan antibodies and its application

抗聚糖抗体生成的新策略及其应用

• 批准号: 22659018
• 负责人: KAWASHIMA Hiroto
• 金额: $ 1.98万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659018/
• 关键词: リンパ球ホーミング; L-セレクチン; 高内皮細静脈; 硫酸化糖鎖; 抗糖鎖抗体; 糖鎖; 免疫学

Anti-carbohydrate monoclonal antibodies(mAbs) are very useful in the functional analysis of complex carbohydrates in vivo. However, such mAbs are difficult to generate, largely because a wide variety of complex carbohydrates is intrinsically expressed in mice and rats and because the antigenicities of glycans are generally poor. In this study, we developed an efficient method for generating anti-carbohydrate mAbs using glycan-synthesizing enzyme-knockout mice in which the glycan structures formed by the missing enzymes should be highly antigenic. As an application of this method, we generated anti-sulfated glycan mAbs using sulfotransferase-deficient mice and found that sulfated N-and sulfated O-glycans function cooperatively in lymphocyte homing and immune surveillance using those mAbs.

抗碳水化合物单克隆抗体 (mAb) 在体内复杂碳水化合物的功能分析中非常有用。然而，此类单克隆抗体很难产生，主要是因为小鼠和大鼠体内固有地表达多种复杂碳水化合物，并且聚糖的抗原性通常较差。在这项研究中，我们开发了一种使用聚糖合成酶敲除小鼠产生抗碳水化合物单克隆抗体的有效方法，其中由缺失的酶形成的聚糖结构应具有高度抗原性。作为该方法的应用，我们使用磺基转移酶缺陷小鼠生成了抗硫酸化聚糖单克隆抗体，并发现硫酸化 N-聚糖和硫酸化 O-聚糖在使用这些单克隆抗体的淋巴细胞归巢和免疫监视中协同发挥作用。

项目成果

Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

外周淋巴结地址素在淋巴细胞归巢至鼻相关淋巴组织和过敏性免疫反应中的重要作用

• 发表时间: 2012
• 作者: Ohmichi Y; Hirakawa J; Imai Y; Fukuda M;Kawashima H
• 通讯作者: Kawashima H

Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

外周淋巴结地址素在淋巴细胞归巢至鼻相关淋巴组织和过敏性免疫反应中的重要作用

• 发表时间: 2011
• 作者: Ohmichi Y; Hirakawa J; Imai Y; Fukuda M;Kawashima H
• 通讯作者: Kawashima H

Novel Anti-Carbohydrate Antibodies Reveal the Cooperative Function of Sulfated N- and O-Glycans in Lymphocyte Homing.

新型抗碳水化合物抗体揭示了硫酸化 N- 和 O- 聚糖在淋巴细胞归巢中的协同功能。

• 发表时间: 2011
• 作者: Hirakawa J; Tsuboi K; Sato K; Kobayashi M; Watanabe S; Takakura A; Imai Y; Ito Y; Fukuda M; Kawashima H
• 通讯作者: Kawashima H

Elevation of rat plasma P-selectin in acute lung injury

急性肺损伤时大鼠血浆P-选择素升高

• 发表时间: 2011
• 作者: Hirose M; Kawashima H; Murai T; Kawakami K; Minamoto
• 通讯作者: Minamoto

Two roles of mucin sulfation

粘蛋白硫酸化的两个作用

• 发表时间: 2010
• 作者: Kawashima H