ALVEOLAR MACROPHAGES AND AIRWAY INFLAMMATION IN ASTHMA

描述(改编自申请者的抽象和具体目标)： 哮喘的特征是呼吸道阻塞，支气管 高反应性和持续性呼吸道炎症。尽管 关于哮喘发病机制的累积数据相对较少 已知从根本上控制免疫的细胞的作用 它调节炎症的发展和消退。 肺泡巨噬细胞(AM)通过以下途径参与哮喘的炎症 促进致炎因子粒细胞-巨噬细胞的产生 巨噬细胞集落刺激因子(GM-CSF)、超氧阴离子或受损 释放抗炎因子白介素10。这个 应用程序假设损害了居民和 在哮喘中招募AM会导致持续的呼吸道炎症，并且 AM的功能上调具体目标是：1)建立 过敏性哮喘患者非刺激性AM和单核细胞功能的研究 在蛋白质和信使核糖核酸水平产生IL-10(和其他相关细胞因子)， 并比较对照组(过敏性鼻炎[非哮喘]受试者， 非过敏性哮喘患者和正常志愿者)；2)建立 节段性抗原攻击或节段性生理盐水攻击对心肌细胞的影响 AM和单核细胞在蛋白质和mRNA水平上产生IL-10 过敏性哮喘患者在挑战后的几个相关时间， 并与对照进行比较；3)确定 AM对重组人[rh]GM-CSF和干扰素-g的作用，或 这些因子的中和抗体，对AM产生IL-10的影响；以及 4)为了确定AM暴露于抗IL-10抗体的影响， 和外源性重组人白介素10，利用产生促炎因子 与哮喘相关的指标(GM-CSF和超氧阴离子)。

DESCRIPTION (Adapted from the applicant's abstract and specific aims): Asthma is characterized by airway obstruction, bronchial hyperresponsiveness, and persistent airway inflammation. Despite the accumulated data regarding the pathogenesis of asthma, relatively little is known about the role of cells which fundamentally control the immune response, and which regulate development and resolution of inflammation. Alveolar macrophages (AM) contribute to inflammation in asthma, via enhanced production of the inflammogenic factors granulocyte-macrophage colony stimulating factor (GM- CSF), and superoxide anion, or by impaired release of the antiinflammatory factor, interleukin (IL)-10. The application hypothesizes that impaired release of IL-10 by resident and recruited AM in asthma leads to persistent airway inflammation, and functional upregulation of AM. The specific aims are: 1) to establish the capacity of unstimulated AM and monocytes of allergic asthmatics to produce IL-10 (and other relevant cytokines) at protein and mRNA levels, and to compare controls (allergic rhinitic [non-asthmatic] subjects, non-allergic asthmatics, and normal volunteers); 2) to establish the effects of segmental antigen challenge or segmental saline challenge on IL-10 production, at the protein and mRNA levels, by AM and monocytes of allergic asthmatics at several relevant times following challenge, and compare to controls; 3) to determine the functional consequences of AM to recombinant human [rh] GM-CSF and interferon (IFN)-g, or neutralizing antibodies to these factors, on AM production of IL-10; and 4) to determine the effects of exposure of AM to antibody against IL-10, and exogenous rhIL-10, using production of pro-inflammatory factors relevant to asthma (GM-CSF and superoxide anion) as indices.