Inhalation Toxicology Core (ITC)

项目总结/摘要：吸入毒理学核心（ITC） 重建一个代表现实生活中的暴露场景的环境是实验研究的关键。 吸入是人体暴露于空气颗粒物（PM）的最具代表性的途径。的 对吸入PM引起的心肺功能障碍的评估是复杂的， 因素，包括PM在其实际暴露形式和剂量下的物理化学性质。创新， 最先进的暴露技术对于可靠地进行体内和体外吸入研究至关重要。 因此，为了补充含有环境污染物的散装颗粒的物理化学表征， 持久性自由基（EPFR），由材料核心（MC）、吸入毒理学核心 (ITC)将生成、输送和表征EPFR气溶胶，用于LSU SRP的体内和体外暴露 项目1和2。创新科技署的使命是提供专业知识、训练、设施及设备， LSU SRP研究人员必须将小鼠或细胞系统暴露于雾化和良好的- 表征的含EPFR的气溶胶，以及评估暴露小鼠的肺功能。这种支持是 1）在实际环境条件下产生稳定的EPFR气溶胶 暴露条件，以及表征可吸入气溶胶的物理化学性质， 项目1和项目2的小鼠呼吸区。由于假设EPFR诱导的心肺 功能障碍涉及在空气-血液界面诱导氧化应激，这是 这种集成的EPFR-气溶胶吸入暴露系统的优点在于，它通过允许 已知尺寸分布的能够到达肺泡的环境相关颗粒的剂量测定 地区2)通过侵入性技术为项目1的小鼠肺功能测试提供支持。ITC将 提供设备，例如flexVent系统，以评估肺功能（阻力和顺应性） 在通过吸入暴露于EPFR气溶胶的小鼠中。3)产生和表征EPFR-气溶胶用于体外 项目1和2的共培养细胞的气液界面（ALI）暴露模型。ALI环境 模拟真实的肺沉积模式和细胞剂量测定，允许合适的细胞和 分子反应。总体而言，ITC出色的研究能力使调查人员能够获得 暴露于以下物质后的体内（功能和生理）和体外（细胞和分子）结果 EPFR-类似暴露条件下的气溶胶和表征方法。因此，为了说明 通过新的补充体内和体外研究， 体外数据集。总之，ITC是一个中心的跨学科平台，定制设计，以适应整体 通过整合从项目3中收集的真实暴露数据、情景和样本，实现中心的目标 并与MC合作进行表征，以及提供曝光方法和专业知识 项目1和2。

Project Summary/Abstract: Inhalation Toxicology Core (ITC) Recreating an environment representative of real-life exposure scenarios is critical for experimental studies. Inhalation is the most representative route of human exposure to airborne particulate matter (PM). The assessment of cardiopulmonary dysfunction induced by inhaled PM is complex and involves a variety of factors, including the physicochemical properties of the PM in its actual exposure form and dose. Innovative, state-of-the-art exposure techniques are essential to reliably conduct in vivo and in vitro inhalation studies. Therefore, to complement the physicochemical characterization of the bulk particles containing environmentally persistent free radicals (EPFRs), as determined by the Material Core (MC), the Inhalation Toxicology Core (ITC) will generate, deliver, and characterize EPFR-aerosols for the in vivo and in vitro exposures of LSU SRP Projects 1 and 2. The mission of the ITC is to provide the expertise, training, facilities and equipment necessary for LSU SRP investigators to expose either mice or cell systems to aerosolized and well- characterized EPFR-containing aerosols, as well as to assess lung function in exposed mice. This support is highlighted through three specific activities: 1) Generating stable EPFR-aerosols under real-life environmental exposure conditions, as well as characterizing the physicochemical properties of the inhalable aerosols in the breathing zone of the mice for Projects 1 and 2. Since it is hypothesized that EPFR-induced cardiopulmonary dysfunction involves induction of oxidative stress at the air-blood interface, a unique innovative advantage of this integrated EPFR-aerosol inhalation exposure system is that it facilitates mechanistic studies by allowing dosimetry of environmentally-relevant particles of known size distribution capable of reaching the alveolar region. 2) Providing support for lung function testing in mice for Project 1 via invasive techniques. The ITC will provide the equipment, for instance the flexiVent system, to assess lung function (resistance and compliance) in mice exposed by inhalation to EPFR-aerosols. 3) Generating and characterizing EPFR-aerosols for in vitro exposure models at the air-liquid interface (ALI) of co-cultured cells for Projects 1 and 2. The ALI environment simulates realistic pulmonary deposition patterns and cellular dosimetry, allowing for suitable cellular and molecular responses. Overall, the outstanding research capabilities of the ITC permits investigators to obtain both in vivo (functional and physiological) and in vitro (cellular and molecular) results following exposures to EPFR-aerosols under similar exposure conditions and characterization methods. Thus, allowing for elucidation of precise EPFR-induced cardiopulmonary dysfunction mechanisms through novel complementary in vivo and in vitro data-sets. In conclusion, the ITC is a central interdisciplinary platform, custom designed to fit the overall goals of the Center by incorporating real-world exposure data, scenarios, and samples collected from Project 3 and characterized in collaboration with the MC, as well as providing the exposure methodology and expertise for Projects 1 and 2.