Underlying mechanisms of schistosome/snail compatibility

血吸虫/蜗牛相容性的潜在机制

• 批准号: 6370996
• 负责人: CHRISTOPHER JEFFREY BAYNE
• 金额: $ 27.26万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6370996
• 关键词: Biomphalaria; Schistosoma mansoni; cell mediated cytotoxicity; cellular immunity; cellular pathology; high performance liquid chromatography; host organism interaction; immunoaffinity chromatography; ion exchange chromatography; microorganism immunology; molecular pathology; phagocytosis; plasma; protein purification; protozoal antigen; schistosomiasis; tissue /cell culture; ultracentrifugation; western blottings

DESCRIPTION (provided by the applicant): The aims of this proposal cover a variety of biochemical and molecular approaches to determine the strain-specific differences between resistant (R) vs. susceptible (S) B. glabratathat would lead to a greater understanding of defense activity in the snail. The PI hypothesizes that: (a) there can be strain-specific differences in the respiratory burst of hemocytes; (b) that sensitivity differences exist in the S and R hemocytes to negative influence of a normal intermediate of the respiratory burst (e.g. chlorinated amines) and; (c) there may be strain differences in induction of specific gene transcripts. Much of the work in this proposal centers on the use of an in vitro assay system for determining sporocyst killing, and the PI has developed ways for selectively inhibiting certain enzymes in O2 and N dependent pathways. Since the last renewal the PI lists 11 manuscripts (published and in press/submitted) and 8 review articles dealing with various aspects of this snail/trematode relationship. Several other papers not directly related are listed that serve as support for demonstrating the PI's expertise in techniques for future studies. Findings during the last funding period led to the understanding that, at least in vitro, both O2 - dependent and -independent mechanisms may play a role in sporocyst killing. This came about after the CMC assay was substantially improved, and finding that H2O2 was involved in killing (although they failed to show differences in ROS production in R and S hemocytes in non-CMC assays). These experiments led to the premise that destruction of sporocysts in resistant snails may be due to a defective myeloperoxidase (MPO) that allows H2O2 to mediate killing, whereas MO hemocytes detoxify H2O2 before it is able to exert its effect fully. The PI also has developed substantial evidence that NO and H2O2 play synergistic roles in sporocyst killing. These results will serve as a basis to explore further these two pathways in sporocyst killing.

描述（由申请人提供）：该提案的目的涵盖 多种生化和分子方法来确定 抗应变特异性差异（R）与易感的B. glabratathat将使人们对国防活动有更深入的了解 蜗牛。 PI假设：（a）可能存在特异性差异 在血细胞的呼吸道爆发中； （b）存在敏感性差异 在S和R血细胞中，正常中间体的负面影响 呼吸爆发（例如氯化胺）和； （c）可能有压力 特定基因转录本的诱导差异。 该提案中的许多工作集中于使用体外测定 确定孢子囊杀死的系统，PI开发了 有选择地抑制O2和N依赖性途径中的某些酶。 自上次续约以来，PI列出了11个手稿（出版并发表 按/提交）和8个涉及各个方面的评论文章 蜗牛/trematode关系。其他几篇无直接相关的论文是 列出的支持证明PI的技术专业知识 用于未来的研究。在最后一个资金期间的发现导致 了解至少在体外，既依赖性和无关 机制可能在孢子囊杀死中发挥作用。这是在CMC之后发生的 测定大大改善，发现H2O2参与了杀戮 （尽管他们未能显示R和S中ROS产生的差异 非CMC分析中的血细胞）。这些实验导致了一个前提 抗性蜗牛中孢子囊的破坏可能是由于有缺陷的 米洛过氧化物酶（MPO）允许H2O2介导杀死，而MO血细胞 在能够充分发挥作用之前将H2O2排毒。 PI还建立了大量证据，表明没有和H2O2播放 在孢子囊杀死中的协同作用。这些结果将作为 进一步探索孢子囊杀死的这两个途径。