Using Nanomaterials to Inhibit Mast Cell/Basophil-Associated Disease

使用纳米材料抑制肥大细胞/嗜碱性粒细胞相关疾病

基本信息

批准号：
7363294
负责人：
Chris L KEPLEY
金额：
$ 29.78万
依托单位：
LUNA INNOVATIONS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-21 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7363294
关键词：
Acute Affect Allergic American Anaphylaxis Antigens Arthritis Arts Asthma Autoantibodies Autoimmune Diseases Basophils Biological Biological Sciences Carbon Cells Condition Development Diagnosis Disease Effector Cell End Point Evaluation Experimental Autoimmune Encephalomyelitis Experimental Models Foundations Fullerenes Goals Growth Human Hypersensitivity IgE In Vitro Inflammation Inflammatory Interdisciplinary Study Joints K/BxN model Kinetics Link Mediating Methodology Modeling Molecular Monitor Multiple Sclerosis Mus Nanotechnology Natural Immunity Pathology Pathway interactions Peptides Principal Investigator Process Property Protein Microchips Public Health Research Science Shapes Signal Pathway Soccer Stem Cell Factor Stimulus Structure Testing cell type chemical property human disease improved in vitro Model in vivo mast cell multidisciplinary nanomaterials novel oligodendrocyte-myelin glycoprotein peripheral blood programs research study response

项目摘要

DESCRIPTION (provided by applicant): Nanotechnology, the use of nanomaterials at the molecular level, is a multidisciplinary scientific field undergoing exponential growth and has broad applications among all divisions of science. One form of nanomaterials, fullerenes, is soccer-ball-shaped carbon cages that can be functionalized and derivatized with a wide array of molecules. Given their unique structure and properties, fullerenes are being investigated as a new and/or improved way to diagnose, monitor, and treat certain conditions. However, no studies have examined the effects these compounds have on the allergic response. Mast cells (MC) and peripheral blood basophils (PBB) are important effector cells that have traditionally been associated with initiating and propagating the allergic response. Recent studies suggest that these cells may also be important regulators of inflammation and innate immunity. We have discovered an unexpected and new mechanism through which the allergic process is inhibited using fullerenes. We hypothesize that fullerene nanomaterials may be a heretofore unrecognized, and potentially useful, way to inhibit diseases that are critically affected by MC and PBB responses. Further, we hypothesize these molecules may be manipulated in such a way that allows them to specifically target MC and PBB. To test these hypotheses we will use a combination of primary human MC and PBB in addition to murine models of human disease including allergy, arthritis, and multiple sclerosis. Our goal is to determine if fullerenes can inhibit the induction and progression of those diseases that have previously been shown to have a large MC/PBB influence. This completely novel research program may lay the foundation for new strategies not only for allergy treatment but for those diseases that are mediated by MC and PBB responses such as arthritis and autoimmune disease. Project Narrative: Allergic diseases, arthritis, multiple sclerosis, and other autoimmune diseases are huge public health problems that affect millions of Americans. These diseases are induced and propagated largely by mast cells and basophils. We have discovered that certain nanomaterials block their noxious effects and thus may be a new way to control those diseases that are largely mediated by these cells types.

描述（由申请人提供）：纳米技术，即在分子水平上使用纳米材料，是一个呈指数增长的多学科科学领域，在所有科学领域都有广泛的应用。纳米材料的一种形式富勒烯是足球形状的碳笼，可以用多种分子进行功能化和衍生化。鉴于其独特的结构和特性，富勒烯正在被研究作为诊断、监测和治疗某些病症的新的和/或改进的方法。然而，没有研究检验这些化合物对过敏反应的影响。肥大细胞 (MC) 和外周血嗜碱性粒细胞 (PBB) 是重要的效应细胞，传统上与引发和传播过敏反应有关。最近的研究表明，这些细胞也可能是炎症和先天免疫的重要调节因子。我们发现了一种意想不到的新机制，通过该机制可以使用富勒烯抑制过敏过程。我们假设富勒烯纳米材料可能是一种迄今为止未被认识的、潜在有用的方法，可以抑制受 MC 和 PBB 反应严重影响的疾病。此外，我们假设这些分子可能以某种方式被操纵，使它们能够特异性地靶向 MC 和 PBB。为了测试这些假设，除了过敏、关节炎和多发性硬化症等人类疾病的小鼠模型外，我们还将使用原代人类 MC 和 PBB 的组合。我们的目标是确定富勒烯是否可以抑制那些先前已被证明对 MC/PBB 影响较大的疾病的诱导和进展。这项全新的研究计划不仅可以为过敏治疗的新策略奠定基础，还可以为由 MC 和 PBB 反应介导的疾病（如关节炎和自身免疫性疾病）的新策略奠定基础。项目叙述：过敏性疾病、关节炎、多发性硬化症和其他自身免疫性疾病是影响数百万美国人的巨大公共卫生问题。这些疾病主要由肥大细胞和嗜碱性粒细胞诱发和传播。我们发现某些纳米材料可以阻止其有害作用，因此可能是控制主要由这些细胞类型介导的疾病的新方法。