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。 呼吸道阻塞、气道高反应性和气道炎症。 虽然哮喘的原因(S)尚不清楚，但我们现在意识到 哮喘是一种慢性炎症性综合征，其共同的病理生物学特征 表现为炎症导致呼吸道高反应性和呼吸道 障碍物。事实上，正是这些共同特征的存在具有 导致了目前NAEP对哮喘的定义，强调哮喘 以可逆性梗阻和高反应性为特征 这两种生理异常都发生在 呼吸道炎症的背景。根据已知的呼吸道存在 炎症，我们对哮喘SCOR竞争的反应一直是 旨在解决我们认为的主要未解答的问题 人类哮喘。具体地说，我们认为我们必须： 定义分子和细胞事件负责启动和 哮喘性呼吸道炎症持续存在。然而，除此之外， 我们必须澄清哮喘性炎症和 哮喘的生理表型特征。 为了解决这些问题，我们组装了一个由5个人组成的SCOR 项目和2个核心单位；每个项目涉及这方面的一个具体方面 引发哮喘、使哮喘持续存在或将炎症与 哮喘的临床表型。我们的核心单位将为患者提供 应计、行政和统计服务。项目1将解决 一氧化氮作为呼吸道指示剂和中介物的作用 哮喘中的梗阻。项目2将研究细胞因子对 分离的人气道平滑肌细胞的收缩反应性 在文化上。在项目3中，我们将进行以下结构定义 新的脂类衍生的下调调节物质，随后定义 他们的新陈代谢，确定他们的生物学行为和 检测它们在哮喘中的表达。项目#4旨在 批判性地检验细胞必须产生起作用的细胞因子的假设 在启动和维持呼吸道炎症中的重要作用 哮喘。该项目还将检验肥大细胞 表达和释放细胞因子的能力本身可能反映了其他微 哮喘呼吸道中的环境因素。在项目5中，我们将 检测非核细胞表面高亲和力IgE受体的表达 哮喘患者吞噬细胞的分离及其信号转导 受体聚集启动的转导。综合来看 从这些SCOR项目中收集的科学见解应该会增强我们的 对哮喘生物学的理解。

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.