Mentored Patient-Oriented Research Career Development Aw

指导以患者为中心的研究职业发展Aw

• 批准号: 6089137
• 负责人: MICHELLE HARKINS
• 金额: $ 12.74万
• 依托单位: UNIVERSITY OF NEW MEXICO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6089137
• 关键词: CD antigens; allergens; alveolar macrophages; antibody receptor; asthma; biomarker; career; cellular pathology; chronic disease /disorder; clinical research; diagnosis design /evaluation; endotoxins; environmental exposure; gene expression; human subject; immunoglobulin E; inflammation; methacholine; nitric oxide; noninvasive diagnosis; nuclear factor kappa beta; receptor expression; respiratory disorder diagnosis; sign /symptom

(Adapted from the applicant's abstract): Asthma is a chronic inflammatory disease of the airways. Monocytes-macrophages are activated and produce increased amounts of inflammatory cytokines in asthmatics when compared to normals. AMs from asthmatics express increased amounts of the low affinity IgE (CD23) receptor. IgE dependent activation of the CD23 receptor on macrophages induces the production of several inflammatory cytokines, including Interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-a) as well as nitric oxide (NO) and cyclic AMP (cAMP). The increased exhaled NO seen in asthmatics is most likely due to enhanced production in epithelial cells and the AM. The investigators hypothesize that the higher percentage of CD23 positive AMs in asthmatics is a marker of AM activation with increased responsiveness to IgE-dependent stimulation. Ligation of this CD23 receptor enhances NFkB, resulting in cytokine production and, either directly or indirectly, increases in NO production. They propose to determine the relationships between IgE complex stimulation of the CD23 positive AMs to increases in NFkB activity and inflammatory cytokine production. They will then determine that the elevated AM CD23 expression and levels of NFkB are markers of inflammation that correlate with exhaled NO measurements, symptom scores, and methacholine challenge in asthmatics when compared to normals. These studies will relate markers of lung inflammation on a cellular level to exhaled NO, a measure of inflammation in the lung. Finding non-invasive ways to monitor the chronic inflammatory process in asthma could then be applied to subsets of asthmatics where CD23 receptor expression may be involved, such as populations exposed to allergen or environmental endotoxin, to identify inflammation and ultimately impact on therapy. For example, if evidence of ongoing inflammation could be documented, then earlier initiation of anti- inflammatory therapy could be instituted in disease modification strategies.

（改编自申请人的摘要）：哮喘是慢性 气道的炎症性疾病。 单核细胞巨噬细胞被激活，并 当哮喘患者中产生增加的炎症细胞因子 与正常人相比。 来自哮喘患者的AM表达增加的低量 亲和力IgE（CD23）受体。 CD23受体的IgE依赖性激活 在巨噬细胞上诱导几种炎性细胞因子的产生， 包括白介素（IL）-1，IL-6，肿瘤坏死因子alpha（TNF-A）AS 以及一氧化氮（NO）和环状放大器（CAMP）。 增加的呼气不 在哮喘患者中看到的很可能是由于上皮的产量增强所致 细胞和AM。 调查人员假设较高的百分比 哮喘患者中的CD23阳性AM是AM激活的标志物，随着增加 对IgE依赖性刺激的反应。 该CD23受体的连接 增强NFKB，导致细胞因子产生，直接或直接 间接地，无生产增加。 他们建议确定 CD23阳性AM与IgE复杂刺激与 NFKB活性和炎性细胞因子产生的增加。 他们会的 然后确定升高的AM CD23表达和NFKB的水平为 炎症的标记与呼气没有测量，症状相关的炎症标记 与正常人相比，哮喘患者中的分数和甲基苯胺挑战。 这些研究将将细胞水平上的肺部炎症标志物与 呼气不，肺部炎症的量度。 寻找非侵入性方法 为了监测哮喘中的慢性炎症过程，可以应用于 CD23受体表达可能涉及的哮喘患者子集，例如 暴露于过敏原或环境内毒素的种群，以识别 炎症并最终影响治疗。 例如，如果证据 可以记录持续的炎症，然后较早开始 炎症疗法可以在疾病修饰策略中进行。