Inhalation Toxicology Core (ITC)

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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.