LUNG LPS BINDING PROTEIN AND ARDS AFTER TRAUMA

描述 (改编自申请者摘要)成人呼吸窘迫综合征 (ARDS)仍然是创伤和死亡的主要原因 危重病人。ARDS被认为是局部性的结果 局部或全身后炎性级联反应的肺激活 损伤，导致肺组织损伤。创伤后或革兰氏阴性 脓毒症时，细菌细胞壁上的内毒素与CD14受体结合 引起炎症介质释放的单个核细胞，如 白介素1、白介素6、肿瘤坏死因子α、 血小板活化因子和一氧化氮。这些调解人被认为 对创伤后ARDS的生理变化负责，或 败血症。脂多糖结合蛋白(LBP)，发现于血清和 本地产生，增强内毒素与CD14受体的结合。这个 申请人此前曾在肺组织中发现LBP生成量升高 在远距离受伤之后。因此，LBP可能会导致过度放大 微量脂多糖存在时的肺炎症反应。 肺LBP产生的调控机制及其在肺损伤中的作用 创伤患者ARDS的病理生理学机制尚不清楚。 目前的建议旨在调查和了解当地政府的作用 创伤后肺组织产生LBP。申请人假设 局部或全身性LBP引起的局部肺产生增加 损伤可能使肺易于发生压倒性的激活 炎症系统导致更大的组织破坏。因此，他 目的明确肺细胞产生LBP的调控因素。 体外以及体内，并确定局部的功能作用 在ARDS的宿主上产生肺LBP对内毒素的反应。 这项赠款提案由两个阶段组成。第一阶段将包括 一份训练计划。通过完成核心课程的课程 并经常与小学和中学导师进行授课， 应聘者将获得强大的知识基础，并获得技术 在分子生物学、细胞生物学和遗传学领域的专业知识。 应聘者将获得先进和复杂的关键知识 在主要导师斯图尔特·C·王博士的指导下， 在做研究提案的时候。第二阶段将重点放在 完成申请的具体目标，并允许应聘者 获得更广泛的科学知识。目标是为了候选人 发展独立的研究领域。(摘要结束)

DESCRIPTION (Adapted from applicants' abstract) The adult respiratory distress syndrome (ARDS) is still a major cause of morbidity and mortality among trauma and critically ill patients. ARDS is believed to be the result of local pulmonary activation of the inflammatory cascade after local or systemic injury, leading to lung tissue damage. After trauma or gram negative sepsis, LPS from the bacterial cell wall binds to CD14 receptors on mononuclear cells causing the release of inflammatory mediators such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), Tumor Necrosis Factor-a (TNF-a), platelet activating factor and nitric oxide. These mediators are believed to be responsible for the physiologic changes seen in ARDS after trauma or sepsis. Lipopolysaccharide binding protein (LBP), found in serum and produced locally, enhances the binding of LPS to CD14 receptor. The applicant has previously found elevated LBP production in pulmonary tissue after distant injury. LBP may therefore contribute to over amplification of the lung inflammatory response in the presence of minute amounts of LPS. The mechanism by which lung LBP production is controlled and its role in the pathophysiology of ARDS in traumatized patients remains unknown. The current proposal seeks to investigate and understand the role of locally produced LBP in lung tissue after trauma. The applicant hypothesizes that elevated local pulmonary production of LBP as a result of local or systemic injury may predispose the lung to an overwhelming activation of the inflammatory system leading to greater tissue destruction. He therefore aims to define the factors regulating LBP production by pulmonary cells in vitro as well as in vivo and to determine the functional role of locally produced pulmonary LBP on host responses to LPS in ARDS. This grant proposal is composed of two phases. The first phase will consist of a training plan. Through the completion of a core curriculum of courses and frequent didactic sessions with both primary and secondary mentors, the candidate will acquire a strong knowledge base as well as obtain technical expertise in the fields of molecular biology, cell biology and genetics. The candidate will gain critical knowledge of advanced and complex techniques under the tutelage of the primary mentor, Dr. Stewart C. Wang, while working on the research proposal. The second phase will focus on completing the specific aims of the application and allow the candidate to gain a broader range of scientific knowledge. The goal is for the candidate to develop independent areas of research. (End of Abstract)