PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA

支气管哮喘的病理生理学

• 批准号: 3336324
• 负责人: Adam Wanner
• 金额: $ 22.9万
• 依托单位: MOUNT SINAI MEDICAL CENTER (MIAMI BEACH)
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3336324
• 关键词: Ascaris; Pasteurella; Pseudomonas aeruginosa; aerosols; antioxidants; asthma; bacterial proteins; body fluid viscosity; bronchial mucus; bronchoconstrictors; bronchodilators; carbohydrate sequence; cilium /flagellum motility; diagnostic respiratory lavage; enzyme linked immunosorbent assay; histology; lectin; leukocyte activation /transformation; membrane activity; muscle contraction; nonblood rheology; perfusion; phagocytes; respiratory airflow measurement; respiratory epithelium; respiratory hypersensitivity; respiratory muscles; sheep; smooth muscle; superoxides; tissue /cell culture; trachea; vascular smooth muscle

Airway hypersecretion occurs in response to various stimuli and is a typical feature of airway disease including bronchial asthma. Since the beginning of this grant in 1978, we have focused our attention on the pathogenesis of allergic mucociliary dysfunction, have characterized some of the mechanisms underlying the associated airway hypersecretion and identified some of the detrimental consequences of this defect. However, an increased quantity and qualitative changes of airway secretions could also play a protective role. The overall objective of this proposal is therefore to determine if surface liquids can protect the airway epithelium, smooth muscle and microvasculature from the effects of noxious stimuli applied from the airway lumen and if this defense function is altered in airway anaphylaxis, a model of asthma. The specific aims of the planned protocols are to demonstrate that respiratory secretions provide a physical barrier against inhaled particulates, a chemical barrier by scavenging oxygen generated by activated luminal phagocytes, and a biological barrier by the ability of secreted glycoconjugates to bind bacterial lectins thereby inhibiting bacterial adhesion to the airway epithelium. Hypersecretion will be produced by a physiologic (cholinergic) stimulus in normal sheep and a pathologic stimulus (antigen) in allergic sheep. The effects of collected airway secretion or airway secretions produced in situ on smooth muscle, ciliary (epithelial cells) and microvascular responses to pharmacologic agents, and oxygen radicals will be assessed in vitro and in vivo. Oxygen radical generation in phagocytes will be induced by stimulating them with bacterial products and phorbol myristate acetate. Bacterial adhesion to glycoconjugates in respiratory secretions and the epithelial glycocalyx will be studied with lectin binding methods. Most of the proposed techniques have been previously used and validated in this and other laboratories. The observations are expected to generate new information on the protective role of respiratory secretions and the alteration of this protection in airway disease. This could form the basis for future studies to identify the responsible chemical constituents of respiratory secretions.

气道高分泌发生在各种刺激中，是一个 气道疾病的典型特征，包括支气管哮喘。 自从 1978年这笔赠款的开始，我们将注意力集中在 过敏性粘膜助力功能障碍的发病机理已经表征了一些 相关气道突出分泌和 确定了该缺陷的一些有害后果。 然而， 气道分泌物的数量和质量变化增加可能 也发挥保护作用。 该提议的总体目标是 因此确定表面液体是否可以保护气道 有害影响的上皮，平滑肌和微脉管系统 刺激从气道管腔应用，如果此防御功能为 气道过敏反应改变，一种哮喘模型。 具体目的 计划的方案是证明呼吸道分泌物 提供对吸入颗粒物的物理屏障，一种化学物质 通过清除由活化的腔吞噬细胞产生的氧气的障碍， 以及由分泌糖缀合物的能力的生物屏障 结合细菌凝集素，从而抑制细菌粘附到气道 上皮。 过度分泌将由生理学产生 （胆碱能）正常绵羊和病理刺激（抗原）刺激 在过敏绵羊中。 收集的气道分泌物或气道的影响 在平滑肌，睫状细胞（上皮细胞）原位产生的分泌物 对药理学剂和氧自由基的微血管反应 将在体外和体内评估。 氧基 吞噬细胞将通过用细菌产物刺激它们和 佛罗宝贝醋酸肉豆蔻酸酯。 细菌对糖缀合物的粘附 将研究呼吸道分泌物和上皮糖卵形 凝集素结合方法。 大多数建议的技术是 先前在此和其他实验室中使用并验证了。这 预计观察结果将产生有关保护性的新信息 呼吸道分泌物的作用和这种保护的改变 气道疾病。 这可能是未来研究的基础 负责的呼吸道分泌物化学成分。