Effects of Inhaled Florida Red Tide Brevetoxins

描述（由申请人提供）：本修订后的计划项目竞争性更新的重点是在实验室模型中揭示佛罗里达赤潮毒素暴露后的作用机制，并为在海滩上暴露的人类提供相关信息。由短凯伦氏菌引起的佛罗里达赤潮每年都会沿着美国墨西哥湾海岸线发生，并向水和空气中释放12种刺激性的天然环境聚醚短毒素，造成有毒后果。毒素拮抗剂也被释放。研究人员已经证明，在最初的5年里，短毒素在吸入暴露的人和动物模型中引起神经毒性、免疫和肺部效应。调查人员应进一步描述吸入暴露于红潮雾化的复杂物质混合物的特征，这些物质在职业、娱乐和易感的人和动物群体中沉积。作用机制和预防以及治疗方法在实验室和现场都得到了加强。要素包括：行政核心；设施核心1“毒素探针和检测”提供QA/QC毒素，衍生物和拮抗剂，分析支持和检测开发；;设施核心2“现场后勤与部署”优化生物和海水的环境监测，部署空气采样器和气象设备，并为研究项目4提供后勤保障。研究项目1“红潮气溶胶的表征”将水华动态与大小、成分和气溶胶效力联系起来，并在数据集中添加气象建模。研究项目2“吸入PbTxs：健康影响与机制”探讨啮齿动物的肺和免疫毒性机制。研究项目3“pbtx诱导的反应机制”探讨了羊模型的吸入效应，包括炎症、纤毛粘膜清除、治疗和预防。研究项目4“雾化红潮PbTx对人类的影响”收集了修订队列的暴露前后数据（化学和生理标准），以及预防/干预试验。利用过去5年优化的研究项目和设施核心协同作用，研究人员将评估PbTx对人类和动物的急性和慢性免疫和肺部影响，以及预防和干预。

DESCRIPTION (provided by applicant): This amended Program Project competitive renewal is focused on revealing mechanisms of action following Florida red tide toxin exposure in laboratory models, and at providing relevant information for humans exposed on beaches. Florida red tides caused by Karenia brevis occur annually along the U.S. Gulf of Mexico coastline, and release 12 irritating natural environmental polyether brevetoxins into water and air with toxic results. Toxin antagonists are also released. The investigators have shown during the first 5 years that brevetoxins elicit neurotoxic, immunologic, and pulmonary effects in inhalation-exposed humans and animal models. The investigators shall further characterize inhalation exposure to the complex mixture of materials aerosolized from red tide, depositing in occupational, recreational, and susceptible human and animal populations. Mechanisms of action and prevention, and therapeutics are intensified foci in laboratory and field alike. Elements include: Administrative Core; Facility Core 1 "Toxin Probes & Assays" provides QA/QC toxins, derivatives and antagonists, analytical support and assay development; ; Facility Core 2 "Field Logistics & Deployment" optimizes environmental monitoring of organism and seawater, deploys air samplers and meterologic gear, and provides logistics for Research Project 4. Research Project 1 "Characterization of Red Tide Aerosols" correlates bloom dynamics with the size, composition, and aerosol potency, and adds meteorlogic modeling to data sets. Research Project 2 "Inhaled PbTxs: Health Effects & Mechanisms" explores pulmonary and immunotoxic mechanisms in rodents. Research Project 3 "Mechanism of PbTx-lnduced Responses" explores inhaled effects in a sheep model, including inflammation, mucociliary clearance, therapeutics and prevention. Research Project 4 "Aerosolized Red Tide PbTx on Humans" collects pre/post exposure data (chemical and physiological criteria) for a revised cohort, as well as prevention/intervention trials. Using the Research Projects and Facility Cores synergy optimized over the past 5 years, the investigators will evaluate acute and chronic immune and pulmonary PbTx effects on humans and animals, as well as prevention and intervention. Lay summary: Florida red tides cause human illness through the airborne release of bioactive chemicals produced during a bloom. Using an interdisciplinary approach, this Program Project employs both laboratory studies and beachside work to understand the human consequences of exposure to aerosolized toxins, to explore therapies for intoxication, and to develop new drugs exploiting red tide bioactive materials.