PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA

气道分泌过多是对各种刺激的反应， 呼吸道疾病的典型特征，包括支气管哮喘。 以来 在1978年开始的这一补助金，我们把注意力集中在 过敏性粘膜纤毛功能障碍的发病机制，已经表征了一些 相关气道高分泌的潜在机制， 确定了该缺陷的一些有害后果。 然而，在这方面， 气道分泌物的量和质的变化增加， 也起到保护作用。 本建议的总体目标是 因此为了确定表面液体是否可以保护气道 上皮、平滑肌和微血管系统免受有害物质的影响 从气道腔施加的刺激，如果这种防御功能是 气道过敏反应的改变，哮喘模型。 的具体目标 计划的方案是证明呼吸道分泌物 提供一个物理屏障，防止吸入颗粒，一种化学物质， 通过清除由激活的管腔吞噬细胞产生的氧来形成屏障， 以及分泌的糖缀合物的能力形成的生物屏障 结合细菌凝集素，从而抑制细菌粘附到气道 上皮 分泌过多是由生理性的 正常绵羊的（胆碱能）刺激和病理刺激（抗原） 过敏的羊 收集的气道分泌物或气道 纤毛平滑肌（上皮细胞）上原位产生的分泌物 和微血管对药物和氧自由基的反应 将在体外和体内进行评估。 氧自由基的产生 吞噬细胞将通过用细菌产物刺激它们而被诱导， 佛波醇肉豆蔻酸酯 细菌对糖复合物的粘附 呼吸道分泌物和上皮糖萼将进行研究， 凝集素结合方法。 大多数提出的技术都是 以前在本实验室和其他实验室使用和验证过。的 预计观察将产生关于保护性的新信息。 呼吸道分泌物的作用和这种保护的改变， 呼吸道疾病 这可以为未来的研究奠定基础， 呼吸道分泌物的化学成分。

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.