The Role of Neutrophils in Hypersensitivity Pneumonitis

中性粒细胞在过敏性肺炎中的作用

• 批准号: 7342785
• 负责人: ELIZABETH ANN FITZPATRICK
• 金额: $ 29.2万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7342785
• 关键词: Alveolitis; Animal Model; Antigens; Automobile Driving; Blood; Breathing; Cells; Detection; Development; Diagnostic; Disease; Educational workshop; Environment; Exposure to; Extrinsic allergic alveolitis; Fibrosis; Goals; Granuloma; Heart; Hypersensitivity; Immune; Immune response; Institutes; Interferons; Interstitial Lung Diseases; Laboratories; Lead; Lung; Mediating; Molecular; Morbidity - disease rate; Mus; Neutrophil Infiltration; Pathogenesis; Patients; Pattern recognition receptor; Play; Pneumonia; Production; Rare Diseases; Rate; Recruitment Activity; Role; Saccharopolyspora; Shapes; Source; Staging; Symptoms; T-Lymphocyte; Testing; Th1 Cells; Toll-Like Receptor 2; United States National Institutes of Health; chemokine; cytokine; genetic risk factor; improved; insight; neutrophil; response; therapy development

DESCRIPTION (provided by applicant): Hypersensitivity Pneumonitis (HP), or extrinsic allergic alveolitis, is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis and granuloma formation that in some patients progresses to fibrosis. The development of fibrosis in HP is associated with high morbidity rates; unfortunately the lack of information on disease pathogenesis has limited the development of therapies to treat the disease. Additionally, the disease is frequently misdiagnosed due to the variability of disease symptoms, differing diagnostic criteria, and a lack of understanding of the environmental antigens and host/genetic risk factors that lead to disease. Our laboratory has been studying the role of IFN( in the development of HP using the Saccharopolyspora rectivirgula (SR) animal model. IFN( is a Th1 cytokine that is required for the development of granulomas in the lungs of mice following repeated exposure to SR. The production of IFN( is important for the expression of T cell chemokines that recruit T cells into the lung following SR exposure; in the absence of IFN(, T cell recruitment and subsequently granuloma formation are reduced. Therefore the cells that produce or regulate IFN( production following SR exposure play a pivotal role in disease pathogenesis. Our studies have revealed that neutrophils are a source of IFN( during the early stages of HP and depletion of neutrophils prior to SR exposure results in decreased IFN( expression. These results suggest that neutrophils play a critical role in the development of HP and understanding the mechanisms that regulate neutrophil recruitment and production of IFN( may provide important new insights into disease pathogenesis. The goals of the proposed study are: Specific Aim1 - to understand the role of neutrophils in driving IFN( production in the lung following SR exposure. Specific Aim 2 - to determine the role of pattern recognition receptors in neutrophil recruitment into the lung.

描述（由申请人提供）：高敏性肺炎（HP）或外部过敏性肺泡炎，是一种间质性肺部疾病，在反复暴露于吸入的环境抗原后会发展出来。该疾病的特征是肺泡炎和肉芽肿的形成，在某些患者中会发展为纤维化。 HP中纤维化的发展与高发病率有关。不幸的是，缺乏有关疾病发病机理的信息限制了治疗疾病的疗法的发展。此外，由于疾病症状的差异，不同的诊断标准以及对导致疾病的环境抗原和宿主/遗传危险因素的了解，这种疾病经常被误诊。我们的实验室一直在研究IFN的作用（在使用Saccharoperysporaypora proctivirgula（SR）动物模型的HP发展中。IFN（IFN（这是Th1细胞因子，是在重复暴露于SR的sr中不存在的TH1细胞中的肉芽肿所必需的Th1细胞（对于SR的产生而言是IFN的重要表达）。 IFN(, T cell recruitment and subsequently granuloma formation are reduced. Therefore the cells that produce or regulate IFN( production following SR exposure play a pivotal role in disease pathogenesis. Our studies have revealed that neutrophils are a source of IFN( during the early stages of HP and depletion of neutrophils prior to SR exposure results in decreased IFN( expression. These results suggest that neutrophils play a critical role在发展HP并了解调节中性粒细胞募集和产生IFN的机制时（可能为疾病发病机理提供重要的新见解。拟议的研究的目标是：特定的目标1-了解中性粒细胞在驱动IFN中的作用（SR暴露后的肺产生。特定目标2-确定模式识别受体在中性粒细胞募集中的作用。