INFLAMMATORY EVENTS INITIATING AND PERPETUATING ASTHMA

哮喘是一种复杂的疾病，其特征是间歇性可逆的 气道阻塞、气道高反应性和气道炎症。 虽然哮喘的原因仍然未知，但我们现在认识到， 哮喘是一种慢性炎症综合征，其常见的病理生物学 表达是炎症，导致气道高反应性和气道炎症。 梗阻 事实上，正是这些共同特征的存在， 导致目前NAEP对哮喘的定义强调哮喘 其特征在于可逆性梗阻和高反应性的 这两种生理异常都发生在 气道炎症的背景。 根据已知的呼吸道 炎症，我们对哮喘中SCOR竞争的反应一直是 旨在解决我们认为是主要的悬而未决的问题， 人类哮喘 具体而言，我们认为我们必须： 定义负责启动的分子和细胞事件 哮喘气道炎症的持续存在。 然而，除此之外， 定义我们必须澄清哮喘炎症和哮喘发作之间的联系。 哮喘的生理表型。 为了解决这些问题，我们组装了一个SCOR，由5个 项目和2个核心单位;每个项目都涉及这方面的一个具体方面 生物学引发哮喘，使哮喘持续存在或将炎症与 临床哮喘表型。 我们的核心单位将提供病人 权责发生制、行政和统计事务。 项目#1将解决 一氧化氮作为气道指标和介质作用 阻塞性哮喘 项目#2将检查细胞因子对 离体人气道平滑肌细胞的收缩反应性 在文化中。 在项目#3中，我们将进行以下结构定义： 新的脂质衍生的下调物质，随后定义 它们的新陈代谢，确定它们的生物学作用， 确定它们在哮喘中的表达 项目#4旨在 批判性地测试假设，细胞必须产生细胞因子， 在启动和维持气道炎症中的重要作用， 哮喘 这个项目还将测试肥大细胞 表达和释放细胞因子的能力本身可能反映了其他微- 哮喘气道中的环境因素。 在项目#5中， 检测非霍奇金淋巴瘤细胞上IgE高亲和力受体的表达， 从哮喘患者中分离的吞噬细胞以及信号 由受体聚集引发的转导。 总的来说， 从这些SCOR项目中收集的科学见解应该可以提高我们的 了解哮喘的生物学。

Asthma is a complex disorder characterized by intermittent reversible airway obstruction, airway hyper-responsiveness and airway inflammation. Although the cause(s) of asthma remain unknown, we now appreciate that asthma is a chronic inflammatory syndrome whose common pathobiological expression is inflammation leading to airway hyperresponsiveness and airway obstruction. In fact it is the presence of these common features which has led to the current NAEP definition of asthma which emphasizes that asthma is characterized by reversible obstruction and hyper-responsiveness of the airways with both of these physiological abnormalities occurring on the background of airway inflammation. Based on the known presence of airway inflammation, our response to the SCOR competition in asthma has been designed to address what we believe are the major unanswered questions in human asthma. In specific we believe that we must: Define the molecular and cellular events responsible for the initiation and perpetuation of asthmatic airway inflammation. However, beyond this definition we must clarify the links between asthmatic inflammation and the physiological phenotype that characterizes asthma. To address these questions we have assembled a SCOR consisting of 5 projects and 2 core units; each project addresses a specific aspect o this biology initiating asthma, perpetuating asthma or linking inflammation to the clinical asthma phenotype. Our core units will provide patient accrual, administrative and statistical services. Project #1 will address the role of nitric oxide as both an indicator and mediator of airway obstruction in asthma. Project #2 will examine the effects of cytokines on the contractile responsiveness of isolated human airway smooth muscle cells in culture. In Project #3 we will undertake the structural definition of novel lipid derived down-regulatory substances followed by a definition of their metabolism, ascertainment of their biological actions and determination of their expression in asthma. Project #4 is designed to test critically the hypothesis that must cells produce cytokines which play an important role in initiating and perpetuating airway inflammation in asthma. This project will also test the hypothesis that the mast cells ability to express and release cytokines may itself reflect other micro- environmental factors in the asthmatic airway. In Project #5 we will examine the expression of the high affinity receptor for IgE on nononuclear phagocytes isolated from patients with asthma as well as signal transduction initiated by receptor aggregation. Taken together the scientific insights gathered from these SCOR projects should enhance our understanding of the biology of asthma.