HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD

嗜血杆菌抗原对 COPD 炎症的调节

• 批准号: 6391238
• 负责人: Sanjay Sethi
• 金额: $ 22.04万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-29 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6391238
• 关键词: Haemophilus influenzae; alveolar macrophages; antigen antibody reaction; bacteria infection mechanism; bacterial antigens; bacterial proteins; biopsy; bronchoscopy; chronic obstructive pulmonary disease; clinical research; computed axial tomography; cytokine; diagnostic respiratory lavage; elastases; enzyme linked immunosorbent assay; human subject; immunocytochemistry; inflammation; membrane proteins; organ culture; pathologic process; polymerase chain reaction; respiratory infections; smoking; thoracic radiography; tobacco abuse

DESCRIPTION (adapted from the applicants' abstract) The contribution of airway inflammation to the pathogenesis of COPD has received increasing recognition. Nontypeable Haemophilus influenzae (NTHI) is the most common bacterial pathogen in the lungs of patients with COPD, and is present in all stages of this disease. NTHI and its components have numerous proinflammatory effects on respiratory tissues. Nonetheless, the role of NTHI as an independent stimulus to inflammation in COPD has not been explored. Alveolar macrophages are critical to host interactions with NTHI. Furthermore, alveolar macrophages respond to inflammatory stimuli distinctly unlike macrophages of extra-pulmonary tissues. Yet interactions of alveolar macrophages with NTHI, and the impact on pathogenesis of COPD, remains unknown. The investigators propose studies designed to gain broader insight into the immunologic mechanisms by which NTHI mediates inflammation in COPD. For all studies, three groups of subjects will be recruited: a) former smokers with COPD; b) former smokers without COPD; and c) healthy non-smokers. In Specific Aim 1, the association between NTHI 'colonization' and levels of inflammatory cells and mediators, in the airway lumen and in tissues, will be determined. Inflammatory cytokines and elastase will be measured in bronchoalveolar lavage (BAL) fluid and inflammatory cells will be enumerated in BAL and in bronchial submucosa. NTHI in the BAL and bronchial biopsies will be detected by culture, PCR and by immunostaining. In Specific Aim 2, the biological effects of outer membrane antigens of NTHI on alveolar macrophage function will be determined. Induction of regulatory cytokines, adhesion molecules and functional capabilities of alveolar macrophages by immunologically active NTHI antigens will be evaluated. Inflammatory and functional parameters will be compared with responses of same-host blood- derived mononuclear phagocytes. Identification of the integral bacterial and host components that contribute to immune-mediated inflammation in COPD will ultimately lead to novel therapeutic strategies to alter disease progression and improve outcome in COPD.

描述（改编自申请人摘要）