Effect of autoantibodies on lung fibroblast phenotype

自身抗体对肺成纤维细胞表型的影响

• 批准号: 6967398
• 负责人: JEAN Cooper PFAU
• 金额: $ 17.63万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-19 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967398
• 关键词: SDS polyacrylamide gel electrophoresis; antibody formation; antigen antibody reaction; asbestos; autoantibody; clinical research; environmental exposure; enzyme linked immunosorbent assay; fibroblast growth factor; human tissue; immunofluorescence technique; immunoglobulin G; lung injury; pathologic process; polymerase chain reaction; pulmonary fibrosis /granuloma; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): Asbestos exposure is associated with pulmonary fibrosis as well as autoimmune responses, including increased antinuclear antibodies. We have recently completed a pilot study of the asbestos-exposed population of Libby MT that suggests that these autoantibodies may be associated with disease progression. The specific aims of this proposal are based on the hypothesis that asbestos exposure leads to the altered expression and presentation by cells within the lung of unique antigens to the immune system, which then mounts an antibody response. These antibodies may then exacerbate chronic inflammatory conditions responsible for asbestos-related disease (ARD) by binding to fibroblasts and increasing their pro-fibrotic activities. The approach is to first demonstrate recognition of fibroblasts by autoantibodies generated in asbestos exposed subjects, then to determine whether asbestos exposure to fibroblasts leads to altered expression of target antigens, and finally to demonstrate that antibodies targeting the fibroblasts can affect pro-inflammatory activities. The long-term goal will be to understand the possible role of autoantibodies in the pathogenesis of lung disease in individuals exposed to a known environmental agent, asbestos. This understanding may be of relevance to other autoimmune diseases where no known inciting agent is known, and therefore these studies will have the potential to provide an approach to prevention and therapeutic modalities.

描述（由申请人提供）：石棉暴露与肺纤维化以及自身免疫反应有关，包括抗核抗体增加。我们最近完成了一项针对 Libby MT 石棉暴露人群的初步研究，表明这些自身抗体可能与疾病进展有关。该提案的具体目标基于这样的假设：石棉暴露会导致肺内细胞对免疫系统的独特抗原的表达和呈递发生改变，然后免疫系统产生抗体反应。这些抗体可能会通过与成纤维细胞结合并增加其促纤维化活性，从而加剧导致石棉相关疾病（ARD）的慢性炎症。该方法首先证明石棉暴露受试者中产生的自身抗体对成纤维细胞的识别，然后确定石棉暴露于成纤维细胞是否会导致靶抗原表达的改变，最后证明针对成纤维细胞的抗体可以影响促炎活性。长期目标是了解自身抗体在暴露于已知环境因素石棉的个体肺部疾病发病机制中的可能作用。这种理解可能与尚无已知诱发因素的其他自身免疫性疾病相关，因此这些研究将有可能提供一种预防和治疗方式的方法。