ALTERED NEUTROPHIL APOPTOSIS /BRONCHOPULMONARY DYSPLASIA

中性粒细胞凋亡改变/支气管肺发育不良

• 批准号: 7027064
• 负责人: BARRY I. WEINBERGER
• 金额: $ 12.81万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-15 至 2008-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7027064
• 关键词: adult human (21+); age difference; apoptosis; artificial respiration; biological signal transduction; biomarker; bronchopulmonary dysplasia; clinical research; cord blood; diagnostic respiratory lavage; disease /disorder etiology; disease /disorder proneness /risk; human subject; inflammation; leukocyte activation /transformation; lung lavage; neutrophil; newborn human (0-6 weeks); phlebotomy; postdoctoral investigator; premature infant human

DESCRIPTION (provided by applicant): This application outlines a career development plan for the applicant who is a practicing neonatologist with an interest in developmental immunology and has the goal of becoming an independent investigator. Under the mentorship of established basic science researchers and a multidisciplinary Advisory Committee, the Principal Investigator will pursue a program of education (coursework, conferences, seminars) and a research project addressing the causation of BPD, a critical issue in neonatal medicine. BPD is a sequence of chronic lung injuries in ventilated premature infants that can be quite severe, resulting in significant morbidity and mortality. Current treatments, including bronchodilator and diuretic therapies, are only palliative. Prevention of BPD using corticosteroids has some benefit, but this has recently been associated with significant and long-term adverse effects. Therefore, it is important to establish methods to identify infants who are at particular risk of developing BPD and to improve preventive therapies. Inflammation and the accumulation of activated neutrophils in the lung play a large part in the pathogenesis of BPD. We hypothesize that reduced clearance of neutrophils from the neonatal lung by apoptosis accounts, in large part, for the severity of inflammatory injuries in BPD, and that this is due to specific alterations in signaling pathways mediating neutrophil activation and apoptosis. To test this hypothesis, blood and lung neutrophil apoptosis in normal and premature infants will be compared with that in adults. Mechanisms underlying reduced apoptosis in neonatal neutrophils will also be analyzed. Quantifying markers for reduced lung neutrophil apoptosis that correlate with the development of BPD may allow us to identify patients at high risk who are good candidates for preventive treatment. The identification of specific pathways mediating apoptosis that are altered in neonatal neutrophils may also suggest preventive therapeutic strategies.

描述（由申请人提供）：该申请概述了职业生涯 申请人的发展计划是一名执业新生儿科医生，具有 对发育免疫学感兴趣，并有成为一名 独立调查员。 在既定基础科学的指导下 研究人员和多学科咨询委员会，校长 研究者将开展教育计划（课程作业、会议、 研讨会）和一个解决 BPD 成因的研究项目，BPD 是一个关键的 新生儿医学问题。 BPD 是一系列慢性肺损伤 早产儿通气可能会非常严重，导致 显着的发病率和死亡率。 目前的治疗方法包括 支气管扩张剂和利尿剂疗法仅起到姑息作用。 预防边缘性人格障碍 使用皮质类固醇有一些好处，但最近这与 具有显着且长期的不良影响。 因此，重要的是 建立方法来识别具有特定发育风险的婴儿 BPD 并改善预防性治疗。 炎症和积聚 肺中活化的中性粒细胞在疾病的发病机制中发挥着重要作用 边缘性人格障碍。 我们假设新生儿中性粒细胞的清除减少 肺细胞凋亡在很大程度上决定了炎症的严重程度 BPD 中的损伤，这是由于信号传导的特定改变所致 介导中性粒细胞活化和凋亡的途径。 为了测试这个 假设，血液和肺中性粒细胞凋亡正常和早产 将婴儿与成人进行比较。 减少的潜在机制 还将分析新生儿中性粒细胞的凋亡。 量化标记 减少与肺中性粒细胞凋亡相关的肺中性粒细胞凋亡 BPD 可以让我们识别出适合接受治疗的高危患者 预防性治疗。 特定介导途径的识别 新生儿中性粒细胞中细胞凋亡的改变也可能表明预防措施 治疗策略。