PATHOPHYSIOLOGY OF BRONCHIAL ASTHMA

支气管哮喘的病理生理学

• 批准号: 3336323
• 负责人: Adam Wanner
• 金额: $ 21.01万
• 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/3336323
• 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; 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.

气道分泌过多是对各种刺激的反应