Determination of the effect of inhaled tyre wear particles on the function and integrity of the human gas-blood barrier

确定吸入轮胎磨损颗粒对人体气血屏障功能和完整性的影响

• 批准号: 2879650
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2879650
• 关键词: Determination; effect; inhaled; tyre; wear

Tyre wear particles (TWP) exhibit physical and chemical properties that depend on the type of tyre and the environmental conditions in which they are generated. Any adverse effects of TWP on the functional-cellular behaviour of target human lung cells will critically depend on their physicochemistry relative to their source and environmental conditions. Objectives: To collect TWP in real time (whist driving) from different types of tyres, under varying conditions (including duration of collection, season, weather conditions, road conditions). To fully characterise the particles - shape, size, surface properties, chemistry To expose primary and in-house transformed primary human lung cells in monoculture and co-culture (to mimic in situ structure) to the TWP, and compare with untreated control and toxic particles (ZnO), pro-inflammatory agents (eg TNF), known bioreactive and internalised particles (charged polystyrene particles). To measure a series of markers of cell function, metabolism and integrity as markers of pathogenicity To measure particle uptake and translocation across epithelial-endothelial gas-blood barrier. An important ongoing component of the PhD will be to fully characterise TWPs (methods above). Cell models will be exposed to TWP particles at the apical epithelial interface, using a wide range of particle concentrations reflecting low, high and chronic exposures, highlighting subtle exposure effects, thresholds of exposure and also any overt effects. Particle uptake and translocation will be examined using the techniques and cell models described above as we have previously published for polystyrene and carbon nanotubes. Use of in vitro models allows us to address the objectives and the 3Rs, and uses small amounts of TWPs (milligrams); larger amounts are costly and difficult to generate. These data will inform future in vivo studies.

轮胎磨损颗粒 (TWP) 表现出的物理和化学特性取决于轮胎的类型及其产生的环境条件。 TWP 对人类目标肺细胞功能细胞行为的任何不利影响将主要取决于其相对于其来源和环境条件的物理化学。 目标：在不同条件（包括收集持续时间、季节、天气条件、道路条件）下从不同类型的轮胎实时（行驶时）收集 TWP。全面表征颗粒 - 形状、大小、表面特性、化学性质 将单一培养和共培养（模拟原位结构）中的原代和内部转化的原代人肺细胞暴露于 TWP，并与未经处理的对照和有毒物质进行比较颗粒（ZnO）、促炎剂（例如TNF）、已知的生物反应性和内化颗粒（带电聚苯乙烯颗粒）。测量一系列细胞功能、代谢和完整性标记物作为致病性标记物 测量颗粒跨上皮内皮气血屏障的摄取和易位。 博士学位的一个重要组成部分将是全面描述 TWP（上述方法）。细胞模型将在顶端上皮界面暴露于 TWP 颗粒，使用反映低、高和长期暴露的各种颗粒浓度，突出微妙的暴露效应、暴露阈值以及任何明显的效应。 将使用上述技术和细胞模型来检查粒子的吸收和易位，正如我们之前针对聚苯乙烯和碳纳米管发表的那样。 使用体外模型使我们能够实现目标和 3R，并使用少量 TWP（毫克）；数额越大，成本越高且难以产生。这些数据将为未来的体内研究提供信息。