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）：此申请概述了职业 申请人的制定计划 对发育免疫学的兴趣，目标是成为 独立研究者。 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 调查人员将遵循教育计划（课程，会议， 研讨会）和一个针对BPD因果关系的研究项目，这是一个关键 新生儿医学问题。 BPD是一系列慢性肺损伤 通风过早的婴儿可能很严重，导致 显着的发病率和死亡率。 当前治疗，包括 支气管扩张剂和利尿剂疗法只是姑息治疗。 预防BPD 使用皮质类固醇有一定的好处，但这最近有关联 产生重大和长期不利影响。 因此，重要的是 建立识别有特殊风险的婴儿的方法 BPD并改善预防疗法。 炎症和积累 肺中激活的中性粒细胞在 BPD。 我们假设从新生儿降低了中性粒细胞的清除率 肺部肺部的肺部很大程度上是炎症的严重程度 BPD中的伤害，这是由于信号传导的特定改变 介导嗜中性粒细胞激活和凋亡的途径。 测试这个 正常和过早的假设，血液和肺中性粒细胞凋亡 婴儿将与成年人进行比较。 降低的机制 新生儿嗜中性粒细胞中的凋亡也将进行分析。 量化标记 为了减少肺中性粒细胞凋亡，与 BPD可能使我们能够识别出高风险的患者，他们是良好的候选人 预防治疗。 介导的特定途径的识别 新生儿嗜中性粒细胞改变的凋亡也可能表明预防性 治疗策略。