LUNG MACROPHAGE FUNCTION IN ENDOTOXIN-INDUCED INJURY

成人呼吸窘迫综合征(ARDS)是一种急性肺病 以顽固性低氧血症和高通透性为特征的损伤 肺水肿。细菌性肺炎是一种并发症，可以 导致败血症，增加ARDS患者的死亡率。 肺泡巨噬细胞(AM)功能下降 在ARDS的几个动物模型中得到证实；相关性 在这种下降和ARDS易感性增加之间 医院获得性肺炎的患者已被提出。 这项研究的目的是定义脑血管疾病的病理生理学 内毒素性肺损伤中AM功能降低及TO 确定肺泡衬里是否调节AM功能 物质和细胞因子可以克服这些减少的肺宿主 防御。我们将通过以下具体措施来解决这个问题 目标： 1.比较肺泡改变的相对重要性 内毒素降低AM功能的环境与AM损伤 致肺损伤。 2.确定牙槽骨改变的重要性 内毒素所见AM功能受损时，衬里材料起作用- 致肺损伤。 3.评价外源性细胞因子对大鼠AM功能的影响 正常动物和内毒素所致肺损伤的动物。 这项建议的具体目标提供了一种智力上的 对我来说是一个研究病理生理学的极具挑战性的机会 一个重要的医学问题。在突出的指导下 当地医学界的研究人员，提出了这项研究 还使我能够评估新的治疗和/或 预防用药改善肺宿主防御能力下降。 除了建议的研究外，综合培训 哈佛大学理科博士学位课程 公共卫生将包括课程作业、实验室培训和 出席研讨会和讲座。我的目标是利用这一点 强化科研训练，成为独立的、有创造力的 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.