Respiratory Effects of Silver and Carbon Nanomaterials (RESAC)

银和碳纳米材料的呼吸效应 (RESAC)

• 批准号: 8288360
• 负责人: Teresa Dorothy Tetley
• 金额: $ 90.35万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-28 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8288360
• 关键词: Affect; Alveolar; Area; Automobile Driving; Biological; Biological Models; Breathing; Carbon; Carbon Nanotubes; Cell model; Cells; Characteristics; Chemicals; Chemistry; Data; Development; Discipline; Dose; Engineering; Environment; Environmental Health; Epithelial Cells; Evaluation; Event; Exposure to; Funding; Grant; Hazard Assessment; Hazardous Substances; Health; Immune; Immune response; In Vitro; Inflammation; International; Knowledge; Life; Link; Liquid substance; Literature; Lung; Lung Inflammation; Marketing; Methods; Modeling; Molecular; Nanotechnology; Occupational; Oxidative Stress; Paper; Pathology; Pathway interactions; Peer Review; Physiological; Property; Publishing; Pulmonary Surfactants; Rattus; Recreation; Research; Risk; Risk Assessment; Route; Safety; Science; Shapes; Silver; Source; Surface; System; Testing; Time; Validation; base; biological systems; body system; chemical property; design; dosimetry; hazard; in vivo; information system analysis; innate immune function; interdisciplinary approach; knowledge base; macrophage; model development; mouse model; multi-scale modeling; nanomaterials; nanoparticle; nanoscale; nanotoxicology; nitrosative stress; novel; oxidation; particle; physical property; prototype; respiratory; response; stem

DESCRIPTION (provided by applicant): Engineered nanomaterials (ENMs) have novel physical and chemical properties, stemming from their nanometer-scale size, and can undergo dynamic changes (e.g., agglomeration, aggregation, and oxidation) when interacting with biological systems. This interaction, thus, has important implications for ENM health effects. The proposed Center grant, entitled 'Respiratory Effects of Silver and Carbon Nanomaterials (RESAC)', focusing on the interaction between ENMs and the lung lining fluid, will use a systematic, integrated, multidisciplinary approach to produce mechanism-driven toxicological data that will be used in a mechanism-based risk analysis framework for ENMs. Main research of the Center will be carried out through three inter-related projects. Project 1 will use cell models to determine ENM physicochemical properties (e.g., size, shape, aspect ratio, chemistry) that dictate the molecular, cellular, and immune reactivities in response to ENM interactions with the lung lining fluid. It is expected that such interaction will also critically impact ENM physicochemical properties, which in turn, will impact on the ENM reactivity with macrophages and epithelial cells. These early cellular- and molecular-level events are crucial in predicting the ultimate fate and pathological consequences of inhaled ENMs, which will be studied in Project 2 using rat and mouse models. Project 2 will examine whether and how inhaled ENMs affect lung surfactant composition and function, induce lung inflammation and lung pathology, generate oxidative stress, penetrate lung cells, and affect the innate immune function of macrophages. Results generated from Projects 1 and 2, along with other relevant data to be collected, will be used in Project 3 that is to define, demonstrate, and test a prototype generalized risk analysis framework for ENMs by implementing, adapting, and expanding available state-of-the-art multi-scale modeling systems for the exposure-to-dose-to-effect sequence. Our new models will mathematically link specific ENM properties (e.g., surface area) to biological effects, allowing the use of most relevant 'dosimetry' in predicting ENM health risks.

描述（由申请人提供）：工程纳米材料（ENM）具有新颖的物理和化学特性，源于其纳米尺寸的大小，并且在与生物系统相互作用时会发生动态变化（例如，聚集，聚集和氧化）。因此，这种相互作用对ENM健康影响具有重要意义。拟议的中心赠款，标题为“银和碳纳米材料的呼吸作用（RESAC）”，重点是ENMS与肺部内衬液之间的相互作用，将使用一种系统的，集成的，多学科的方法来产生机制驱动的毒理学数据，这些方法将是这种毒理学数据用于ENM的基于机制的风险分析框架。该中心的主要研究将通过三个相互关联的项目进行。项目1将使用细胞模型来确定ENM物理化学特性（例如，大小，形状，纵横比，化学），该特性决定了与ENM与肺部内膜相互作用的响应分子，细胞和免疫反应性。预计这种相互作用还将严重影响ENM理化特性，这反过来会影响巨噬细胞和上皮细胞的ENM反应性。这些早期的细胞和分子水平事件对于预测吸入ENM的最终命运和病理后果至关重要，该eNM将在项目2中使用大鼠和小鼠模型进行研究。项目2将检查吸入ENM是否以及如何影响肺表面活性剂组成和功能，诱导肺部炎症和肺病理学，产生氧化应激，穿透肺细胞并影响巨噬细胞的先天免疫功能。项目1和2产生的结果以及要收集的其他相关数据将在项目3中使用，该项目将通过实施，适应和扩展可用的状态 - 用于暴露对剂量到效应序列的图像多尺度建模系统。我们的新模型将在数学上将特定的ENM属性（例如表面积）与生物学作用联系起来，从而可以在预测ENM健康风险中使用最相关的“剂量法”。