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Novel therapeutic strategy for ulcerative colitis by hard capsule contained with IgG Fc binding protein

IgG Fc结合蛋白硬胶囊治疗溃疡性结肠炎的新策略

基本信息

批准号：
16590631
负责人：
OGATA Haruhiko
金额：
$ 2.24万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590631/
关键词：
mucosal immunology mucosal defense drug delivery system IgG Fc binding protein mucin 粘膜制御

项目摘要

Mucus released from goblet cells is important in intestinal mucosal defense, and mucin glycoproteins are thought to be major components of mucus. Recently, we identified and cloned another component of human colonic mucus, IgG Fc binding protein (Fc gamma BP). Fc gamma BP is immunologically distinct from known Fc gamma receptors and its structure contains repeated cysteine rich unit sequences resembling those present in mucins. We assessed the tissue distribution of Fc gamma BP, its binding activity in various body fluids, and its ability to inhibit complement mediated haemolysis. Immunohistochemical localization of Fc gamma BP, using monoclonal antibodies against Fc gamma BP (K9 or K17) and labelled IgG, was conducted in various mucin producing tissues : colon, small intestine, stomach, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, conjunctiva, and cervix uteri. The binding activity of Fc gamma BP in mucus extracted from colon, gastric juice, bile, nasal disch … More arges, saliva, sputum, and tears was also examined by immunodotblot and immunoprecipitation using these monoclonal antibodies. Inhibition of complement mediated haemolysis by Fc gamma BP was investigated using sheep red blood cells (SRBC) and anti-SRBC IgG.The immunohistochemical study revealed that mucin secreting cells in the colon, small intestine, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, and cervix uteri contained Fc gamma BP, and immunodotblot and immunoprecipitation analysis using IgG and monoclonal antibodies demonstrated that the fluids secreted by these cells were capable of binding IgG. Mucin producing cells of the conjunctiva did not express Fc gamma BP molecules or bind to IgG. The surface mucus cells in the stomach were variably positive for Fc gamma BP. Perhaps because of proteolytic degradation, Fc gamma BP in gut lavage fluid did not have IgG binding activity, although this activity was present in the mucus covering the colon. Fc gamma BP suppressed complement mediated haemolysis of SRBC.Fc gamma BP is widely expressed on mucosal surfaces and in external secretions. It is functionally intact in several fluids. These findings lend support to the concept that Fc gamma BP is an important component of mucosal immunological defences. Less

从杯状细胞释放的粘液在肠粘膜防御中是重要的，并且粘蛋白糖蛋白被认为是粘液的主要组分。最近，我们鉴定并克隆了人结肠粘液的另一种组分，IgG Fc结合蛋白（Fc γ BP）。Fc γ BP在免疫学上不同于已知的Fc γ受体，并且其结构含有类似于粘蛋白中存在的那些的重复的富含半胱氨酸的单元序列。我们评估了Fc γ BP的组织分布、其在各种体液中的结合活性及其抑制补体介导的溶血的能力。使用抗Fc γ BP（K9或K17）的单克隆抗体和标记IgG，在各种产生粘蛋白的组织中进行Fc γ BP的免疫组织化学定位：结肠、小肠、胃、胆囊、胆囊管、胆总管、支气管、颌下腺、结膜和子宫颈。从结肠、胃液、胆汁、鼻分泌物和胃粘膜中提取的Fc γ BP的结合活性 ...更多信息还使用这些单克隆抗体通过免疫斑点印迹和免疫沉淀检查了阿尔热、唾液、痰和泪液。用绵羊红细胞（SRBC）和抗SRBC IgG研究了Fc γ BP对补体介导的溶血的抑制作用，免疫组化结果显示，结肠、小肠、胆囊、胆囊管、胆总管、支气管、颌下腺和子宫颈的粘液分泌细胞中含有Fc γ BP，用IgG和单克隆抗体的免疫斑点印迹和免疫沉淀分析表明，这些细胞分泌的液体能够结合IgG。结膜的产生粘蛋白的细胞不表达Fc γ BP分子或与IgG结合。胃中的表面粘液细胞为Fc γ BP阳性。可能由于蛋白水解降解，肠道灌洗液中的Fc γ BP不具有IgG结合活性，尽管这种活性存在于覆盖结肠的粘液中。Fc γ BP抑制补体介导的SRBC溶血。Fc γ BP广泛表达于粘膜表面和外分泌物中。它在几种液体中功能完整。这些发现支持Fc γ BP是粘膜免疫防御的重要组分的概念。少