Mucosal Immune Barrier in Infection and Inflammation

感染和炎症中的粘膜免疫屏障

• 批准号: 7053395
• 负责人: Keith E Mostov
• 金额: $ 128.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2008-09-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053395
• 关键词: bacteria infection mechanism; clinical research; human tissue; inflammation; mucosa; mucosal immunity; wound healing

DESCRIPTION (provided by applicant): Exposed mucosal surfaces, such as the respiratory, gastrointestinal, and genitourinary surfaces, are lined primarily by a single layer of epithelial cells. This cell layer serves at least two primary functions in the mucosal immune system. First, it is a barrier to the entry of the >95% of infectious agents that enter through mucosal surfaces, as well as a barrier to allergens and other noxious agents. Mucosal infectious diseases include such high priority agents as AIDS and other sexually transmitted diseases, numerous opportunistic infections and emerging and re-emerging diseases, and bio-terrorist agents. Second, in response to these pathologic agents, inflammatory and immune cells are recruited and cross the epithelial barrier, following a chemotactic gradient. This Program Project presents a multidisciplinary and highly interactive approach to these problems. The Project and Core leaders combine a great deal of experience and diverse insights and techniques. Our experimental systems range from in vitro cell culture to genetically modified whole animals, though we focus on lung epithelium as an exemplary mucosal, and Pseudomonas aeruginosa as an exemplary mucosal pathogen. The integrity of the epithelial monolayer is essential to its mucosal immune function. The epithelial monolayer has sophisticated wound-healing mechanisms to maintain its integrity. Project 1 concentrates on the basic mechanisms of epithelial wound healing. Project 2 focuses on how wound healing is altered by P. aeruginosa and closely parallels Project 1. Projects 3 and 4 focus on the movement of inflammatory cells across the epithelial monolayer into the lumen. Project 3 considers the transmigration of the polymorphonuclear neutrophil, specifically the role of CD47 and the ligand for Mac-l. Project 4 focuses on the role of matrix metalloproteases (MMPs) in chemotaxis of inflammatory cells into the lumen. All four projects are supported by all three cores. Core A is administrative. Core B, Cell Isolation and Culture, provides primary lung epithelial cells for all projects. Core C provides Live Cell Multiphoton and Confocal Imaging, which will be vital to all projects. There is very extensive interaction and collaboration through out. For instance, Projects 1, 2 and 4 all utilize mice knocked-out for certain MMPs.

描述（由申请人提供）：暴露的粘膜表面，例如呼吸道，胃肠道和泌尿生殖器表面，主要由单个上皮细胞衬里。该细胞层在粘膜免疫系统中至少具有两个主要功能。首先，它是通过粘膜表面进入的> 95％的传染剂进入的障碍，也是过敏原和其他有害特工的障碍。粘膜传染病包括诸如艾滋病和其他性传播疾病，众多机会主义感染以及新兴和重新出现疾病的高优先型药物以及生物恐怖分子。其次，响应于这些病理剂，在趋化梯度后，募集炎症和免疫细胞并越过上皮屏障。该计划项目为这些问题提供了多学科和高度互动的方法。该项目和核心领导者结合了很多经验以及各种见解和技术。我们的实验系统范围从体外细胞培养到转基因的整体动物，尽管我们专注于肺上皮作为示例性粘膜，再加上铜绿假单胞菌作为模范粘膜病原体。上皮单层的完整性对于其粘膜免疫功能至关重要。上皮单层具有复杂的伤口修复机制，可维持其完整性。项目1集中​​于上皮伤口愈合的基本机制。项目2的重点是如何通过铜绿假单胞菌改变伤口愈合，并与Project1。项目3和4相似。项目3考虑了多形核中性粒细胞的迁移，特别是CD47和配体对MAC-L的作用。项目4的重点是基质金属蛋白酶（MMP）在炎症细胞趋化细胞中的作用。这四个项目均得到所有三个核心的支持。核心A是管理。细胞分离和培养的核心为所有项目提供原发性肺上皮细胞。 Core C提供了活细胞多光子和共聚焦成像，这对所有项目至关重要。整个互动和协作都非常广泛。例如，项目1、2和4都利用某些MMP的小鼠淘汰了小鼠。