LUNG MACROPHAGE FUNCTION IN ENDOTOXIN-INDUCED INJURY

成人呼吸窘迫综合征（ARDS）是一种急性肺 以顽固性低氧血症和高渗透性为特征的损伤 肺水肿 细菌性肺炎是一种并发症 导致ARDS患者的败血症和死亡率增加。 肺泡巨噬细胞（AM）功能的降低已被证实是一种重要的细胞因子。 在几种ARDS动物模型中得到证实; 这种减少和ARDS易感性增加之间的关系 患者的医院获得性肺炎已被提出。 这项研究的目的是确定的病理生理学， 内毒素诱导的肺损伤中AM功能降低， 确定是否用肺泡衬里调节AM功能 材料和细胞因子可以克服这些减少的肺宿主 的防御合作. 我们将通过以下具体措施解决此问题 目的： 1. 比较肺泡变化的相对重要性 环境与AM损伤在降低内毒素中AM功能中的作用- 导致肺损伤。 2. 确定肺泡改变的重要性 内衬材料在内毒素中所见的受损AM功能中发挥作用- 导致肺损伤。 3. 评价外源性细胞因子对AM功能的影响 正常动物和具有内毒素诱导的肺损伤的动物。 这项建议的具体目标提供了一个智力上的 对我来说是一个挑战性的机会来研究 一个重要的医学问题。 在著名的 当地医学界的研究人员， 也使我能够评估新的治疗和/或 预防剂以改善降低的肺宿主防御。 除了建议的研究，综合训练 在哈佛医学院攻读理学博士学位 公共卫生将包括课程，实验室培训， 参加研讨会和讲座。 我的目标是用这个 强化研究训练，成为一个独立的，创造性的 研究员

Adult Respiratory Distress Syndrome (ARDS) is a form of acute lung injury characterized by refractory hypoxemia and high permeability pulmonary edema. Bacterial pneumonia is a complication which can result in sepsis and increased mortality rates in ARDS patients. A decrease in alveolar macrophage (AM) function has been demonstrated in several animal models of ARDS; a correlation between this decrease and an increased susceptibility of ARDS patients to nosocomial pneumonia has been proposed. The goal of this research is to define the pathophysiology of decreased AM function in endotoxin-induced lung injury and to determine whether modulating AM function with alveolar lining material and cytokines can overcome these decreased pulmonary host defenses. We will address this problem with the following Specific Aims: 1. Compare the relative importance of changes in the alveolar milieu vs. damage to the AM in decreasing AM function in endotoxin- induced lung injury. 2. Determine the importance that alterations in the alveolar lining material play in the impaired AM function seen in endotoxin- induced lung injury. 3. Evaluate the effects of exogenous cytokines on AM function in normal animals and in those with endotoxin-induced lung injury. The specific aims of this proposal provide an intellectually challenging opportunity for me to investigate the pathophysiology of an important medical problem. Under the direction of prominent researchers in the local medical community, the proposed research also allows me to evaluate the potential of new therapeutic and/or prophylactic agents to improve decreased pulmonary host defenses. In addition to the proposed research, the comprehensive training program for the Doctor of Science degree at the Harvard School of Public Health will include coursework, laboratory training, and attendance at seminars and lectures. It is my goal to use this intensive research training to become an independent, creative researcher.