PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA

呼吸道高分泌是对各种刺激的反应，是一种 包括哮喘在内的呼吸道疾病的典型特征。自.以来 从1978年这笔赠款开始，我们把注意力集中在 过敏性粘液纤毛功能障碍的发病机制，有一定的特点 相关的呼吸道高分泌和 确定了这一缺陷的一些有害后果。然而， 呼吸道分泌物的数量和质量的增加可以 也起到了保护作用。这项提议的总体目标是 因此，要确定表面液体是否可以保护呼吸道 有害物质对上皮、平滑肌和微血管的影响 从气道腔施加的刺激，如果这种防御功能 哮喘的一个模型--呼吸道过敏反应的改变。的具体目标 计划中的方案是为了证明呼吸道分泌物 提供物理屏障，防止吸入颗粒物、一种化学物质 通过清除激活的腔内吞噬细胞产生的氧气来屏障， 和生物屏障，通过分泌糖偶联物的能力 结合细菌凝集素从而抑制细菌与呼吸道的黏附 上皮组织。高分泌量会由生理上的 正常绵羊胆碱能刺激和病理刺激(抗原) 在过敏的绵羊身上。收集的呼吸道分泌物或呼吸道的影响 在平滑肌、纤毛(上皮细胞)上原位产生的分泌物 和微血管对药物的反应，以及氧自由基 将在体外和体内进行评估。氧自由基的产生 吞噬细胞将通过细菌产品和刺激来诱导 佛波酯。细菌对糖结合物的粘附性 呼吸道分泌物和上皮性糖萼将用 凝集素结合法。大多数被提议的技术已经被 以前在本实验室和其他实验室中使用和验证。这个 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及其保护作用的改变 呼吸道疾病。这可能成为未来研究的基础，以确定 呼吸道分泌物中负责的化学成分。

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.