Respiratory Effects of Silver and Carbon Nanomaterials (RESAC)

银和碳纳米材料的呼吸效应 (RESAC)

• 批准号: 8468709
• 负责人: Teresa Dorothy Tetley
• 金额: $ 86.78万
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468709
• 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）因其纳米级尺寸而具有新颖的物理和化学性质，并且在与生物系统相互作用时可以经历动态变化（例如，附聚、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。拟议的中心拨款题为“银和碳纳米材料的呼吸效应（RESAC）”，重点关注 ENM 与肺衬里液之间的相互作用，将使用系统的、综合的、多学科的方法来生成机制驱动的毒理学数据，这些数据将用于 ENM 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、长宽比、化学性质），这些特性决定了响应 ENM 与肺内膜液体相互作用的分子、细胞和免疫反应性。预计这种相互作用也将严重影响 ENM 的理化性质，进而影响 ENM 与巨噬细胞和上皮细胞的反应性。这些早期细胞和分子水平的事件对于预测吸入 ENM 的最终命运和病理后果至关重要，项目 2 将使用大鼠和小鼠模型对其进行研究。项目2将研究吸入的ENM是否以及如何影响肺表面活性剂的组成和功能，诱发肺部炎症和肺部病理，产生氧化应激，渗透肺细胞，并影响巨噬细胞的先天免疫功能。项目 1 和 2 生成的结果以及要收集的其他相关数据将用于项目 3，即通过实施、调整和扩展可用的状态来定义、演示和测试 ENM 的原型广义风险分析框架。用于暴露-剂量-效应序列的最先进的多尺度建模系统。我们的新模型将在数学上将特定的 ENM 特性（例如表面积）与生物效应联系起来，从而允许使用最相关的“剂量测定”来预测 ENM 健康风险。