SCHISTOSOME - SNAIL COMPATIBILITY: UNDERLYING MECHANISMS

血吸虫与蜗牛的相容性：潜在机制

• 批准号: 3126571
• 负责人: CHRISTOPHER JEFFREY BAYNE
• 金额: $ 21.8万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-30 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3126571
• 关键词: Biomphalaria; SDS polyacrylamide gel electrophoresis; Schistosoma mansoni; alternatives to animals in research; cell mediated cytotoxicity; cellular immunity; cellular pathology; communicable disease transmission; endopeptidases; enzyme activity; hamsters; host organism interaction; membrane activity; microorganism immunology; molecular pathology; phagocytosis; proteolysis; protozoal antigen; schistosomiasis; tissue /cell culture; western blottings

On account of the considerable burden placed on human populations by Schistosoma mansoni in schistosome-endemic areas, an understanding of the basic mechanisms responsible for transmission of these human parasites via their intermediate molluscan hosts is desirable. This research seeks to understand how it is that a miracidium larva is able to penetrate a snail and transform into a sporocyst without eliciting aggressive defensive responses. Since individual snails (Biomphalaria glabrata) may be susceptible or resistant to individual S. mansoni, the cellular and molecular bases for this variability are to be sought. At least some components of this mollusc's internal defense system are subject to modulation by trematode parasites and by stress. Therefore, following treatments proven to modulate hemocyte activity, the influence of such altered states will be evaluated in assays of snail resistance. Assays include in vitro phagocytosis, cytoadherence and cell mediated cytotoxicity, and in vivo resistance to S. mansoni. An hypothesis that the compatibility of schistosome and snail is due in part to mimicry of carbohydrate epitopes will be tested using polyclonal sera, with antigens subjected to proteolytic degradation, and known carbohydrate epitopes used as competing ligands. Substantively improved quantification of in vitro cytotoxicity will allow us to determine whether resistant plasma accelerates sporocyst killing. Another hypothesis implicating lysosomally-derived, plasma enzymes in modulating resistance will be tested both in vivo and in vitro using plasma from appropriately treated snails and defined enzymes. A functional role will be sought for a 50 kD plasma component found uniquely in strains of snail which are resistant to the PR1 strain of S. mansoni. Polyclonal antisera will be used in efforts to block effector functions, and the affinity-purified plasma component will be evaluated for its ability to facilitate recognition and/or cytotoxic hemocyte effector functions. Finally, the relevance of a novel alpha-macroglobulin-like protein in snail plasma to outcomes of snail - schistosome encounters will be investigated.

由于 曼氏血吸虫在血迹 - 流行地区，对 负责通过这些人寄生虫传播的基本机制 他们的中间软体动物宿主是可取的。 这项研究试图 了解Miracidium幼虫能够穿透蜗牛是如何 并转变为孢子囊而不引起侵略性防御 回答。 由于单个蜗牛（Biomphalaria glabrata）可能是 易感或抗药性或抗药性 要寻求这种变异性的分子碱基。 至少一些 Mollusc内部防御系统的组成部分受 通过Trematode寄生虫和应力调节。 因此，跟随 被证明可以调节血细胞活性的疗法，这种影响 改变状态将在蜗牛耐药性测定中进行评估。 测定 包括体外吞噬作用，细胞保化和介导的细胞 细胞毒性和对曼氏链球菌的体内耐药性。 一个假设 血块和蜗牛的兼容性部分归因于模仿 碳水化合物表位将使用抗原进行多克隆血清测试 经过蛋白水解降解，并使用已知的碳水化合物表位 作为竞争配体。 实质上改善了体外的定量 细胞毒性将使我们能够确定抗性等离子体是否 加速孢子囊杀死。 另一个假设涉及 将测试溶酶体衍生的血浆酶调节抗性 在体内和体外使用经过适当处理的蜗牛的血浆 并定义的酶。 50 kD等离子体将寻求功能作用 在对PR1有抵抗力的蜗牛菌株中发现的成分 S. Mansoni菌株。 多克隆抗血清将用于阻止 效应子功能，亲和纯化的等离子体组件将是 评估其促进识别和/或细胞毒性的能力 血细胞效应子功能。 最后，小说的相关性 蜗牛等离子体中的α-巨球蛋白样蛋白 - 蜗牛结果 - 将调查阴谋体相遇。