Inhalation Toxicology Core (ITC)

项目摘要/摘要：吸入毒理学核心(ITC) 重建一个代表真实暴露场景的环境对于实验研究至关重要。 吸入是人类接触空气颗粒物(PM)的最具代表性的途径。这个 吸入PM所致心肺功能障碍的评估是复杂的，涉及多种 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是必不可少的。 因此，为了补充环境中含有的大块颗粒的物理化学表征 持久性自由基(EPFR)，由吸入毒理学核心物质核心(MC)测定 (ITC)将为LSU SRP的体内和体外暴露产生、交付和表征EPFR气雾剂 项目1和2.贸易中心的任务是提供专门知识、培训、设施和设备 路易斯安那州立大学SRP调查人员有必要将小鼠或细胞系统暴露于雾化和良好的- 对含有EPFR的气雾剂进行了表征，并评估了暴露小鼠的肺功能。这一支持是 通过三个具体活动突出：1)在真实环境下产生稳定的EPFR气溶胶 暴露条件，以及表征空气中可吸入气溶胶的物理化学性质 项目1和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，这是一种独特的创新优势 这种集成的EPFR-气雾剂吸入暴露系统通过允许 已知大小分布的能够到达肺泡的环境相关颗粒物的剂量测定 区域。2)通过侵入性技术为项目一小鼠肺功能检测提供支持。国际贸易委员会将 提供设备，例如FlexiVent系统，以评估肺功能(抵抗力和顺应性) 吸入EPFR气雾剂的小鼠。3)体外EPFR气雾剂的制备和表征 项目1和项目2的共培养细胞的气液界面暴露模型。ALI环境 模拟真实的肺沉积模式和细胞剂量测定，允许适当的细胞和 分子反应。总体而言，国贸中心出色的研究能力使调查人员能够获得 暴露在体内(功能和生理)和体外(细胞和分子)的结果 EPFR-气溶胶在相似的暴露条件和表征方法下。因此，允许澄清 EPFR诱导的心肺功能障碍机制的体内和体外新互补研究 体外数据集。总而言之，ITC是一个中央跨学科平台，定制设计以适应整体 通过纳入从项目3收集的真实世界暴露数据、场景和样本来实现中心的目标 与MC合作，并提供曝光方法和专业知识 对于项目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.