Macrophages, sugars and innate immunity in chronic lung inflammation

慢性肺部炎症中的巨噬细胞、糖和先天免疫

• 批准号: nhmrc : 145779
• 负责人: Prof Gary Anderson
• 金额: $ 27.55万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/macrophages-sugars-innate-lung-inflammation/101420
• 关键词: Macrophages; sugars; innate; immunity; chronic

This project is about a new idea to treat severe asthma, chronic obstructive lung disease (COPD) and sudden worsening of these diseases (exacerbations). Asthma and COPD are very common. Asthma afflicts approximately 10 % of all Australians and kills approximately 700 annually. COPD will be the third most common cause of death worldwide by 2010 (WHO) and costs more that $ AUS 10 Billion annually. The highest risk of death and greatest costs are associated with severe asthma and exacerbations. Our idea, which is based on extensive animal data, is that these diseases can be treated by blocking the activity of proteins that allow a cell called the lung macrophage to grow, become activated, proliferate and survive. These proteins are called CSF-1 and GM-CSF and they belong to a larger class of proteins called colony stimulating factors (CSFs) Macrophages are important because they can rapidly respond to bacteria, viruses and fungi that can infect the lungs of asthma and COPD patients. Infections cause exacerbations. Normally, macrophages release a number of molecules called mediators that rouse a strong defensive reaction- a process called innate immunity. For example macrophages signal for a cell type called the neutrophil, which is a very efficient bacteria killer, to flood into the lung. However, these same cells can cause serious lung damage if the response is too strong or persistent. Macrophages and neutrophils need CSFs to work properly so blocking CSFs prevents lung damage. Although we now already know that blocking CSFs can prevent and reverse lung inflammation we still need to know a great deal more in order to know if this approach will be useful to treat people in the future. Our project is therefore all about understanding the fine detail of how CSFs can damage the lung. The importance of the project is that our work may lead to entirely new, and much more effective, treatments for people suffering from asthma and COPD.

这个项目是关于治疗严重哮喘，慢性阻塞性肺疾病（COPD）和这些疾病的突然恶化（恶化）的新思路。哮喘和慢性阻塞性肺病很常见。大约10%的澳大利亚人患有哮喘，每年导致大约700人死亡。到2010年，慢性阻塞性肺病将成为全球第三大常见死因（世卫组织），每年造成的损失将超过100亿澳元。最高的死亡风险和最大的费用与严重哮喘和急性发作有关。我们的想法是，基于大量的动物数据，这些疾病可以通过阻断蛋白质的活性来治疗，这种蛋白质允许一种叫做肺巨噬细胞的细胞生长、被激活、增殖和存活。这些蛋白质被称为CSF-1和GM-CSF，它们属于更大的一类蛋白质，称为集落刺激因子（csf）。巨噬细胞很重要，因为它们可以快速响应可以感染哮喘和COPD患者肺部的细菌、病毒和真菌。感染会导致病情恶化。正常情况下，巨噬细胞会释放大量被称为介质的分子，引发强烈的防御反应——这一过程被称为先天免疫。例如，巨噬细胞向一种叫做中性粒细胞的细胞发出信号，中性粒细胞是一种非常有效的细菌杀手，它会涌入肺部。然而，如果反应过于强烈或持续，这些细胞也会造成严重的肺损伤。巨噬细胞和中性粒细胞需要csf才能正常工作，因此阻断csf可防止肺损伤。虽然我们现在已经知道阻断csf可以预防和逆转肺部炎症，但我们仍然需要知道更多，以便知道这种方法在未来是否对治疗人们有用。因此，我们的项目都是关于了解csf如何损害肺部的细节。这个项目的重要性在于，我们的工作可能会为哮喘和慢性阻塞性肺病患者带来全新的、更有效的治疗方法。