Complement activation of intestinal epithelial cells

肠上皮细胞的补体激活

• 批准号: 138632-2010
• 负责人: Stadnyk, Andrew
• 金额: $ 2.4万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=505977
• 关键词: Complement; activation; intestinal; epithelial; cells

The boundary between your tissues and the lumen in your intestines is a thin sheet of cells called epithelial cells. From this interface with the environment epithelial cells must balance being tolerant of food and some bacteria yet respond with inflammation to other pathogenic bacteria. We think that one way the epithelial cells know to respond to pathogenic bacteria is because another natural defence system becomes activated directly by the bacteria. This defence system is called complement and is intended to make bacteria more easily killed by white blood cells and directly kills bacteria by forming pores on their surface. Complement activation requires a number of proteins be split. We have discovered that epithelial cells have the receptors for these split complement proteins but we do not know what happens to the cells as a result of binding the split proteins. This grant will explore the idea that the split complement proteins cause the epithelial cells to initiate inflammation. This includes recruiting white blood cells from the blood into the gut tissues. Epithelial cells have other molecules on their surface to protect them from the pores that complement assembles. We expect that binding the split complement proteins will result in epithelial cells making more of these protective molecules, to minimize damage by complement on the gut itself. These ideas will be tested using epithelial cells in petri dishes but our findings will then be validated in mice. Mice are chosen because they can be made deficient in complement proteins. The significance is that failures in the communication between epithelial cells and complement may compromise the host response to pathogenic bacteria, possibly causing or worsening disease in man and animals.

你的组织和肠腔之间的边界是一层薄薄的细胞，叫做上皮细胞。在与环境的交界面上，上皮细胞必须平衡对食物和某些细菌的耐受性，同时对其他致病菌产生炎症反应。我们认为，上皮细胞知道对致病菌作出反应的一种方式是，另一种自然防御系统被细菌直接激活。这种防御系统被称为补体，旨在使细菌更容易被白细胞杀死，并通过在细菌表面形成毛孔直接杀死细菌。补体激活需要许多蛋白质被分裂。我们已经发现上皮细胞有这些分裂补体蛋白的受体，但我们不知道结合分裂蛋白后细胞会发生什么。这项资助将探索分裂的补体蛋白导致上皮细胞引发炎症的想法。这包括从血液中招募白细胞进入肠道组织。上皮细胞表面有其他分子保护它们不受气孔的影响。我们预计，结合分裂的补体蛋白将导致上皮细胞产生更多的这些保护性分子，以尽量减少补体对肠道本身的损害。这些想法将在培养皿中使用上皮细胞进行测试，但我们的发现将在小鼠身上得到验证。选择老鼠是因为它们可以使补体蛋白缺乏。重要的是，上皮细胞和补体之间通信的失败可能会损害宿主对致病菌的反应，可能导致或恶化人类和动物的疾病。