PATHOGENESIS OF VIRAL PROLIFERATIVE BRONCHIOLITIS

病毒性增殖性细支气管炎的发病机制

• 批准号: 6169831
• 负责人: Lucille London
• 金额: $ 16.68万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6169831
• 关键词: Reoviridae; acute bronchitis; cytokine; disease /disorder etiology; disease /disorder model; histopathology; laboratory mouse; lung injury; model design /development; pathologic process; pneumonia; pulmonary fibrosis /granuloma; respiratory epithelium; respiratory infections; virus genetics

DESCRIPTION (Adapted from the applicant's abstract): Bronchiolitis obliterans with organizing pneumonia (BOOP) is a term for a long observed, but unclassified pattern of acute lung injury. In humans, BOOP is characterized by fibrosis of small airways with fibrous extension into the alveolar spaces with preservation of alveolar ducts and walls. It is frequently associated with a peribronchiolar organizing pneumonia. The lesions may also be accompanied by lipid-laden foamy alveolar macrophages trapped in the air spaces by the fibrosis and by a T cell rich lymphocytic interstitial infiltrate in the regions of the lung directly affected by the lesion. Also, necrosis and sloughing of epithelial cells has been observed and is thought to result in the partial alveolar collapse seen in human BOOP. While BOOP can be associated with documented viral and bacterial infections, many cases are not associated with known causes and are thus classified as idiopathic. Little is known concerning the pathogenesis and treatment of BOOP since no animal models were available for this disorder. The investigators are the first to establish an experimental animal model for this disease. In this model, CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions which closely resemble the histopathological picture of human BOOP. In addition, the development of BOOP lesions in CBA/J mice is virus strain specific. The central hypothesis of this proposal is that "Disruption of the epithelial basement membrane determines the susceptibility to fibrosis". The investigators propose to characterize the host and/or viral factors (both immune and non-immune cellular populations) that result in initiation of damage to the basement membrane and relate these finding to the development of fibrosis.

描述（改编自申请人的摘要）：支气管炎 有组织性肺炎（BOOP）的闭塞性是长期观察到的术语， 但是未分类的急性肺损伤模式。 在人类中，嘘声是 以纤维伸展为纤维化的特征 牙槽空间，可保存牙槽和壁。 这是 经常与组织肺炎组织肺炎有关。 这 病变也可能伴随着富含脂质的泡沫肺泡巨噬细胞 被纤维化和富含T细胞的淋巴细胞捕获在空气空间中 直接影响的肺部区域的间质浸润 病变。 同样，已经观察到上皮细胞的坏死和裂缝 并被认为会导致人类的部分牙槽塌陷 嘘声。 虽然嘘声可以与有记录的病毒和细菌有关 感染，许多病例与已知原因无关，因此 归类为特发性。 关于发病机理和 由于没有动物模型可用于这种疾病，因此boop的处理。 研究人员是第一个建立实验动物模型的人 对于这种疾病。 在此模型中，感染了葡萄病毒血清型的CBA/J小鼠 1/菌株lang发展出泡沫病变，非常类似于 人类繁荣的组织病理学图片。 此外，发展 CBA/J小鼠中的BOOP病变是病毒菌株的特异性。 中心假设 该提议是“上皮地下膜的破坏 确定对纤维化的敏感性”。研究人员建议 表征宿主和/或病毒因子（免疫和非免疫因素 细胞种群）导致对地下室造成损害 膜并将这些发现与纤维化的发展联系起来。