ANTIBACTERIAL DEFENSE FACTORS OF URINARY BLADDER MUCOSA

膀胱粘膜的抗菌防御因子

• 批准号: 2142617
• 负责人: Michael Raymond Ruggieri
• 金额: $ 13.4万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-20 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2142617
• 关键词: Escherichia coli; affinity chromatography; animal tissue; antibody; atomic absorption spectrometry; bactericidal immunity; cell adhesion; complementary DNA; enzyme linked immunosorbent assay; gel filtration chromatography; genetic library; high performance liquid chromatography; human tissue; immunocytochemistry; laboratory rabbit; molecular cloning; mucins; mucosa; nucleic acid probes; pathologic process; postmortem; secretion; urinary bladder; urinary bladder epithelium; urinary tract infection

Much of the previous work on the role of bacterial adherence in urinary tract infection has focused on bacterial factors (adhesins) with relatively less attention given to the role of host defense mechanisms. We have recently demonstrated a defective antiadherence activity of bladder extracts (mucin) from patients with recurrent urinary tract infection. Thus in these patients, there may be a functional defect and/or decrease in a factor in the mucin that is responsible for its antibacterial adherence property. A substantial body of animal work indicates that the initial first line defense against invading microorganisms in the urinary tract is the antiadherence activity of the surface mucin layer. Therefore, the structure, chemical composition and physiology of the mucosal surface is such that bacteria are denied attachment to the luminal surface allowing urinary flow to wash them away. A novel approach to the treatment of bladder infection would be the identification and clinical use of agents that either mimic the natural antiadherence activity of the bladder mucosa, augument production of the endogenous mucosal defense factor(s) or break these attachments and thus effectively limit the infection process. The objectives of this proposal are to characterize active antibacterial defense factors of the bladder mucosa and to determine the role these factors play in pathologic states of increased infection susceptibility. To accomplish these goals antibodies are produced to the natural antibacterial defense substance(s) from both bovine and human bladder mucosa. These antibodies are used to develop quantitative and immunohistochemical localization assays in order to determine how these factors come into being and whether they are secreted by an apparenty non-secreting transitional epithelial surface. In addition these antibodies are eventually used to screen expression libraries in order to develop cDNA probes for these factors. The long range goal is to use this insight to develop novel therapies for bladder infection directed at preventing bacterial adherence in patents who are at high risk of developing urinary tract infection. In order to begin develop novel agents it is necessary to first gain an understanding of both the biochemical mechanisms by which bacteria attach to the bladder and the biochemical properties of the natural antibacterial defense factor(s) in bladder muchin.

先前关于细菌依从性在尿中作用的大部分工作 道感染的重点是细菌因子（粘附） 对宿主防御机制的作用的关注相对较少。 我们最近表现出有缺陷的抗基础活性 来自复发尿路患者的膀胱提取物（粘蛋白） 感染。 因此，在这些患者中，可能存在功能缺陷 和/或粘蛋白负责其的因素的减少 抗菌依从性。 大量动物工作 表明最初的一线防御反对入侵 尿路中的微生物是 表面粘蛋白层。 因此，结构，化学组成和 粘膜表面的生理学使细菌被拒绝 附着在腔表面上，允许尿流洗涤它们 离开。 一种新的膀胱感染治疗方法是 鉴定和临床使用的药物可以模仿 膀胱粘膜的自然抗抑制活性，八月 产生内源性粘膜防御因子或破坏这些 附件，从而有效地限制了感染过程。 该提案的目标是表征主动抗菌 膀胱粘膜的防御因素，并确定这些作用 在感染易感性提高的病理状态下的因素。 为了实现这些目标，抗体是自然的 牛和人膀胱的抗菌防御物质 粘膜。 这些抗体用于开发定量和 免疫组织化学定位测定法，以确定这些方法 因素出现了，是否被明显分泌 非分泌过渡上皮表面。 另外这些 抗体最终用于按顺序筛选表达式库 为这些因素开发cDNA探针。 远程目标是使用 这种开发针对膀胱感染的新型疗法的见解 防止具有高风险的专利细菌依从性 发展尿路感染。为了开始发展小说 代理人有必要先了解两者 细菌附着在膀胱上的生化机制和 天然抗菌防御因子的生化特性 膀胱巨星。