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GROWTH FACTOR SECRETION IN DUST INDUCED LUNG DISEASE

粉尘引起的肺病中的生长因子分泌

基本信息

批准号：
2152920
负责人：
RALPH M SCHAPIRA
金额：
$ 5.25万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-08-01 至 1995-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2152920
关键词：
alveolar macrophages asbestos catalase diagnostic respiratory lavage electron microscopy free radical oxygen glucose oxidase histopathology hydroxyl radical lung injury platelet derived growth factor pneumoconiosis pollution related respiratory disorder pulmonary fibrosis /granuloma superoxide dismutase xanthine oxidase

项目摘要

The alveolar inflammation, injury and fibrosis characteristic of the pneumoconioses are thought to be mediated by the alveolar macrophage. Asbestos has long been known to be a cause of pulmonary fibrosis and the development of lung lesions following inhalation of asbestos fibers in the rat has been well characterized. The alveolar macrophage can secrete cytokines such as platelet-derived growth factor (PDGF) which has mitogenic and chemotactic effects on mesenchymal cells such as fibroblasts and induces collagen synthesis. We hypothesize that lung macrophages exposed to inhaled dusts secrete growth factors such as PDGF which mediate the development of pulmonary fibrosis. The grant proposal seeks to establish factors that modify the secretion of PDGF by rat lung macrophages exposed to dusts in vitro such as matrix components (collagen, laminin, fibronectin), concentration and physicochemical nature of particles, exposure times in culture, or reactive oxygen intermediates. Reactive oxygen intermediates in vitro will be generated by the xanthine-xanthine oxidase and glucose-glucose oxidase systems and selectively blocked by various scavengers such as catalase, superoxide dismutase or the hydroxyl radical (OH) scavenger dimethylthiourea. In addition, macrophages will be exposed to asbestos treated with iron chelators which prevent asbestos-mediated OH production (the Fenton reaction) to determine whether OH generation modulates PDGF secretion by macrophages. Rats will be exposed to inhaled asbestos and "asbestos substitutes" and macrophages isolated and cultured to measure PDGF secretion. Lung injury will be assessed by light and electron microscopy. Rats will be exposed to asbestos coated with iron chelators and PDGF secretion compared to uncoated fibers. Systemic treatment of rats prior to asbestos exposure with iron chelators, catalase, superoxide dismutase, and colchicine will be performed to determine whether these pharmacological interventions modify lung injury or PDGF secretion by macrophages compared to exposed rats not treated with these interventions.

肺泡炎症、损伤及纤维化的特点