HAEMOPHILUS ANTIGEN REGULATION OF INFLAMMATION IN COPD

嗜血杆菌抗原对 COPD 炎症的调节

• 批准号: 6285816
• 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/6285816
• 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（改编自申请人的摘要） 气道炎症对COPD发病机理的贡献 得到了越来越多的认可。 不可能的流感嗜血杆菌（NTHI）是 COPD患者肺中最常见的细菌病原体，IS 出现在该疾病的各个阶段。 NTHI及其组件有很多 对呼吸组织的促炎作用。 尽管如此，nthi的作用 作为对COPD炎症的独立刺激，尚未探索。 肺泡巨噬细胞对于与NTHI的相互作用至关重要。 此外，肺泡巨噬细胞对炎症刺激有何反应 与肺外组织的巨噬细胞不同。 然而肺泡的相互作用 具有NTHI的巨噬细胞，以及对COPD发病机理的影响，仍然存在 未知。 研究人员提出的研究旨在获得更广泛的见解 进入免疫机制，NTHI介导COPD中的炎症。 对于所有研究，将招募三组受试者：a）以前 吸烟者患有COPD； b）没有COPD的前吸烟者； c）健康的非吸烟者。 在特定目标1中，nthi“殖民化”与水平之间的关联 气道管腔和组织中的炎症细胞和介体将是 决定。 炎性细胞因子和弹性酶将在 将列举支气管肺泡灌洗（BAL）流体和炎症细胞 在BAL和支气管层中。 BAL和支气管活检中的NTHI 将通过培养，PCR和免疫染色来检测。 在特定的目标2中， NTHI外膜抗原对肺泡的生物学作用 将确定巨噬细胞功能。 诱导调节细胞因子， 通过肺泡巨噬细胞的粘附分子和功能能力 将评估具有免疫活性的NTHI抗原。 炎症和 功能参数将与同一宿主血液的反应进行比较 衍生的单核吞噬细胞。 鉴定整体细菌和 导致免疫介导的COPD炎症的宿主成分将 最终导致了改变疾病进展的新型治疗策略 并改善COPD的结果。