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（改编自申请人的摘要） 气道炎症在 COPD 发病机制中的作用 受到越来越多的认可。 不可分型流感嗜血杆菌 (NTHI) 是 慢性阻塞性肺病患者肺部最常见的细菌病原体 存在于本病的各个阶段。 NTHI 及其组件具有众多 对呼吸组织的促炎作用。 尽管如此，NTHI 的作用 作为 COPD 炎症的独立刺激因素尚未被探索。 肺泡巨噬细胞对于宿主与 NTHI 的相互作用至关重要。 此外，肺泡巨噬细胞对炎症刺激有明显的反应 与肺外组织的巨噬细胞不同。 然而肺泡的相互作用 巨噬细胞与 NTHI 以及对 COPD 发病机制的影响仍然存在 未知。 研究人员提出旨在获得更广泛见解的研究 研究 NTHI 介导 COPD 炎症的免疫机制。 对于所有研究，将招募三组受试者： 患有慢性阻塞性肺病的吸烟者； b) 没有慢性阻塞性肺病的前吸烟者； c) 健康的非吸烟者。 在具体目标 1 中，NTHI“定植”与 气道腔和组织中的炎症细胞和介质将被 决定。 炎症细胞因子和弹性蛋白酶将在 支气管肺泡灌洗 (BAL) 液和炎症细胞将被计数 在 BAL 和支气管粘膜下层中。 BAL 和支气管活检中的 NTHI 将通过培养、PCR 和免疫染色来检测。 在具体目标 2 中， NTHI外膜抗原对肺泡的生物学效应 将确定巨噬细胞的功能。 诱导调节性细胞因子， 粘附分子和肺泡巨噬细胞的功能能力 将评估免疫活性 NTHI 抗原。 炎症和 功能参数将与相同宿主血液的反应进行比较 衍生的单核吞噬细胞。 完整细菌的鉴定和 导致慢性阻塞性肺病免疫介导炎症的宿主成分将 最终导致改变疾病进展的新治疗策略 并改善慢性阻塞性肺病的治疗结果。