Multiwalled-Carbon Nanotube Properties and Macrophage Proinflammatory Responses

多壁碳纳米管特性和巨噬细胞促炎症反应

基本信息

批准号：
8625977
负责人：
Paul Pantano
金额：
$ 45.9万
依托单位：
UNIVERSITY OF TEXAS DALLAS
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8625977
关键词：
Address Adverse effects Animal Model Animals Asbestos Biological Bovine Serum Albumin Caliber Carbon Nanotubes Cell Extracts Cell membrane Cell model Cells Chemistry Collaborations Conflict (Psychology)Cytoplasm Cytosol Environment Event Experimental Designs Foundations Health Human Hydrogen Bonding Image Inflammation Interleukin-1 Lasers Lead Length Literature Lung Measures Membrane Membrane Lipids Mesothelioma Methods Microscopy Modeling Nanotubes Outcome Phagocytes Phagolysosome Pluronics Polyacrylamide Gel Electrophoresis Powder dose form Preparation Production Property Proteins Protocols documentation Publishing Pulmonary Fibrosis Reporting Research Resolution Review Literature Route Scanning Sodium Dodecyl Sulfate Surface Surveys System TNF gene Time Toxic effect Vendor Work base cell injury cellular imaging cytokine cytotoxicity in vivo macrophage multi walled carbon nanotube novel strategies public health relevance rapid technique research study response three-dimensional modeling uptake

项目摘要

The production and use of multi-walled carbon nanotubes (MWNTs) are rapidly increasing world-wide, despite the possible adverse effects they may have on human health. Of particular concern are reports that MWNTs can cause pulmonary fibrosis in lab animals that may lead to mesothelioma, similar to asbestos. The literature is conflicted regarding what physical features of MWNTs cause phagocytic cells to release proinflammatory cytokines that precede pulmonary fibrosis. It has also been suggested that phagolysosome membrane damage caused by MWNTs is a key event leading to cytokine release by phagocytic cells, but what MWNT properties cause damage is also not clear. The broad objectives of the research proposed here are to better understand whether MWNT length and extent of dispersion are factors leading to cytokine release by phagocytic cells and to explore a relatively new approach, laser scanning confocal Raman microscopy, to assess whether MWNTs damage the phagolysosomal membrane en route to eliciting cytokine release. There are two specific aims to achieve the objectives of the proposal: Specific aim 1: To quantify the amount of MWNTs taken up by two types of phagocytic cells and to correlate the uptake with MWNT length, dispersant, agglomeration, toxicity, and the release of proinflammatory cytokines. Two different MWNT types will be studied, long and short. For each type, two dispersions will be prepared with the dispersants bovine serum albumin or Pluronic(R) F-108, highly dispersed and agglomerated. The experimental design will use a new method to measure the actual amount of the MWNTs that accumulate inside cultured phagocytic cells, followed by measuring the release of two cytokines, TNF-¿ and IL-1¿. The results of this aim will, for the first time, correlate the actual amount of MWNTs inside phagocytic cells with MWNT length, type of dispersant, agglomeration, toxicity, and the release of proinflammatory cytokines. Specific aim 2: To determine the subcellular distribution of MWNTs and potential phagolysosome damage by laser scanning confocal Raman microscopy (LSCRM). LSCRM, a relatively new approach to cell imaging, can directly locate MWNTs inside cells by their unique Raman signature and be used to reconstruct 3D models from confocal sections showing the subcellular distribution of MWNTs. LSCRM can also image membranes in cells based on the C-H bond Raman scattering of membrane lipids. With this combination of capabilities it may be possible to determine whether MWNTs taken up by cells damage the phagolysosome membrane and redistribute throughout the cytosol. Results from this aim should help address whether MWNT length and state of dispersion are factors in damaging the phagolysosome membrane.

尽管在全球范围内，多壁碳纳米管（MWNT）的生产和使用正在迅速增加多壁碳纳米管可能对人类健康产生的不利影响值得特别关注。与文献中的石棉类似，可导致实验动物肺纤维化，从而导致间皮瘤。关于 MWNT 的物理特征导致吞噬细胞释放促炎性物质的问题存在矛盾也有人认为，吞噬溶酶体膜是肺纤维化之前的细胞因子。 MWNT 造成的损伤是导致吞噬细胞释放细胞因子的关键事件，但是 MWNT 的作用是什么？属性造成的损害也不清楚。这里提出的研究的总体目标是为了更好。了解 MWNT 长度和分散程度是否是导致细胞因子释放的因素吞噬细胞并探索一种相对较新的方法，激光扫描共焦拉曼显微镜，评估 MWNT 是否会在引发细胞因子释放的过程中损伤吞噬溶酶体膜。实现该提案目标的两个具体目标是：具体目标 1：量化两种类型吞噬细胞摄取的 MWNT 量并将吸收与 MWNT 长度、分散剂、团聚、毒性和释放相关联将研究两种不同的 MWNT 类型，即长的和短的。分散体将用分散剂牛血清白蛋白或 Pluronic(R) F-108 制备，高度分散实验设计将使用一种新方法来测量实际数量。 MWNT 在培养的吞噬细胞内积累，然后测量两种细胞因子的释放，肿瘤坏死因子-¿和 IL-1¿这一目标的结果将首次与内部 MWNT 的实际数量相关联。吞噬细胞的 MWNT 长度、分散剂类型、团聚、毒性和释放促炎细胞因子。具体目标 2：确定 MWNT 和潜在吞噬溶酶体的亚细胞分布激光扫描共焦拉曼显微镜 (LSCRM) 是一种相对较新的损伤检测方法。细胞成像，可以通过其独特的拉曼特征直接定位细胞内的 MWNT，并用于从共焦切片重建 3D 模型，显示 LSCRM 的亚细胞分布。还可以根据膜脂质的 C-H 键拉曼散射对细胞膜进行成像。结合多种能力，有可能确定细胞吸收的 MWNT 是否会损害细胞吞噬溶酶体膜并在整个细胞质中重新分布。这一目标的结果应该有助于解决这个问题。 MWNT长度和分散状态是否是破坏吞噬溶酶体膜的因素。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Importance of Evaluating the Lot-to-Lot Batch Consistency of Commercial Multi-Walled Carbon Nanotube Products.

DOI：
10.3390/nano10101930
发表时间：
2020-09-27
期刊：
Nanomaterials (Basel, Switzerland)
影响因子：
0
作者：
Huynh MT;Veyan JF;Pham H;Rahman R;Yousuf S;Brown A;Lin J;Balkus KJ Jr;Diwakara SD;Smaldone RA;LeGrand B;Mikoryak C;Draper R;Pantano P
通讯作者：
Pantano P

Use of Raman spectroscopy to identify carbon nanotube contamination at an analytical balance workstation.