EOSINOPHILS IN PULMONARY FIBROTIC DISEASE

慢性阻塞性肺疾病中炎症和纤维化的发病机制 特发性肺纤维化仍有待充分阐明，以及 需要对这种进行性疾病进行有效的治疗。计划中的 研究基于一系列发现，表明嗜酸性粒细胞 重要的、以前未被认识到的细胞参与者 肺纤维化的发病机制。通过敏感的染色技术， 嗜酸性粒细胞在肺中可见明显数量。 人和小鼠特发性肺纤维化中的间质 肺炎症和纤维化模型。嗜酸性粒细胞，它们有 作用正常的伤口愈合反应，是几种纤维化的来源 细胞因子。对人体样本的分析显示嗜酸性粒细胞占主导地位 几乎90%的细胞表达细胞因子的mRNA转录本 转化生长因子-β1。计划中的研究将利用这两种方法 评估嗜酸性粒细胞在人类和小鼠组织和细胞中的作用 肺纤维化的发展。对人体组织和 细胞将评估通过以下方法获得的组织中嗜酸性粒细胞的流行率 用活检的人肺组织进行开胸肺活检将评估 嗜酸性粒细胞和其他细胞作为促炎来源的贡献 和纤维化细胞因子。嗜酸性粒细胞阐述各种不同 纤维化细胞因子及其调控机制将是 用分离的人类嗜酸性粒细胞进行研究。研究利用小鼠模型 对博莱霉素诱导的肺部炎症和纤维化的评价 嗜酸性粒细胞在颞叶中作为纤维化细胞因子来源的作用 肺损伤的演变和研究可能的干预措施 为了阻止嗜酸性粒细胞的招募和激活 肺内白细胞病变。这些对人类和 实验性肺纤维化的目的是确定 嗜酸性粒细胞在炎症和纤维化反应中的作用 在肺纤维化疾病中。了解这些角色和 研究可能调节嗜酸性粒细胞功能的方式 将在更广泛的背景下进行，以描绘 导致肺纤维化的进行性炎症过程。从… 这些研究对肺纤维化的发病机制有了新的认识 将获得疾病和潜在的新的治疗方法 将对肺纤维化进行评估。

The pathogenesis of the inflammation and fibrosis that develop in idiopathic pulmonary fibrosis remains to be fully delineated, and effective treatments for this progressive disease are needed. The planned studies are based on a series of findings indicating that eosinophils are important, previously unrecognized, cellular participants in the pathogenesis of pulmonary fibrosis. With sensitive staining techniques, eosinophils are demonstrable in appreciable numbers in the pulmonary interstitium in both human idiopathic pulmonary fibrosis and in murine models of pulmonary inflammation and fibrosis. Eosinophils, which have role normal wound healing responses, are sources of several fibrogenic cytokines. Analyses of human samples demonstrate eosinophils to account for almost 90% of cells expressing mRNA transcripts for cytokine transforming growth factor-beta1. The planned studies will utilize both human and murine tissues and cells to evaluate the roles of eosinophils in the development of pulmonary fibrosis. Studies with human tissues and cells will evaluate the prevalence of eosinophils in tissues obtained by open lung biopsy with biopsied human lung tissues will evaluate the contributions of eosinophils and other cells as source pro-inflammatory and fibrotic cytokines. The capacity of eosinophils to elaborate various fibrotic cytokines and the mechanisms regulating that elaboration will be studied with isolated human eosinophils. Studies utilize the murine model of bleomycin-induced pulmonary inflammation and fibrosis to evaluate the roles of eosinophils as sources of fibrotic cytokines in the temporal evolution of pulmonary injury and to investigate potential interventions to interrupt the recruitment and activation of eosinophils and other leukocytes pulmonary lesions. These investigations of human and experimental pulmonary fibrosis will aim to define the roles of eosinophils in the progression of the inflammatory and fibrotic responses in pulmonary fibrotic diseases. Understanding these roles and investigating modalities that may modulate the functioning eosinophils will be pursued in the broader context of delineating the evolution of the progressive inflammatory process that leads to pulmonary fibrosis. From these studies, new understanding of pathogenesis of pulmonary fibrotic diseases will be obtained and potential new therapeutic approaches of pulmonary fibrosis will be evaluated.