Macrophages, sugars and innate immunity in chronic lung inflammation

该项目是关于治疗严重哮喘、慢性阻塞性肺疾病（COPD）和这些疾病突然恶化（急性加重）的新想法。哮喘和COPD非常常见。哮喘折磨着大约10%的澳大利亚人，每年导致大约700人死亡。到2010年，COPD将成为全球第三大常见死因（WHO），每年花费超过100亿澳元。死亡风险最高、费用最高的是严重哮喘和哮喘加重。我们的想法是基于广泛的动物数据，这些疾病可以通过阻断蛋白质的活性来治疗，这些蛋白质允许一种称为肺巨噬细胞的细胞生长，激活，增殖和存活。这些蛋白质被称为CSF-1和GM-CSF，它们属于一个更大的蛋白质类别，称为集落刺激因子（CSF），巨噬细胞是重要的，因为它们可以迅速响应细菌，病毒和真菌，可以感染哮喘和COPD患者的肺部。感染会导致病情加重。正常情况下，巨噬细胞会释放一系列称为介质的分子，这些分子会引起强烈的防御反应，这一过程称为先天免疫。例如，巨噬细胞发出信号，让一种叫做嗜中性粒细胞的细胞涌入肺部，嗜中性粒细胞是一种非常有效的细菌杀手。然而，如果反应太强或持续，这些细胞可能会导致严重的肺损伤。巨噬细胞和中性粒细胞需要CSF才能正常工作，因此阻断CSF可以防止肺损伤。虽然我们现在已经知道阻断CSF可以预防和逆转肺部炎症，但我们仍然需要了解更多，以便知道这种方法是否对未来的治疗有用。因此，我们的项目是关于了解CSF如何损害肺部的细节。该项目的重要性在于，我们的工作可能会为哮喘和COPD患者带来全新的、更有效的治疗方法。

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.