NEUTROPHIL RECRUITMENT IN LPS-INDUCED AIRWAY DISEASE

描述（摘自研究者摘要） 该提案的总体目标包括一个促进职业发展的计划 杰西卡·克莱坎普博士的发展，同时了解一个调查 内毒素介导的气道损伤的基本成分-中性粒细胞 招募到肺部。 Klekamp博士的长期职业目标是发展 教育，研究技能和经验，成为独立的 能够在生物医学领域做出有意义贡献的医生-科学家 科学 这个奖项，将使她能够实现她的直接目标， 进一步加深了她对细胞在分子水平上相互作用的理解 通过课程学习，获得分子生物学新的研究技能， 继续研究白细胞和内皮细胞的粘附 分子。 这一职业发展计划将在理想的情况下进行 美国国立卫生研究院支持的环境气道专业中心的环境 疾病，与博士大卫A。施瓦茨是她的导师， 对于这个专业的中心。 这种环境为Klekamp博士提供了 资源和充分利用科学专门知识， 对环境性肺病研究的贡献。 拟议 一项研究项目调查了早期致病事件， 中性粒细胞从血管间隙到气道的运动，在一个 建立内毒素诱导的小鼠气道疾病模型。 虽然角色 白细胞/内皮细胞粘附分子在中性粒细胞募集中的作用 体循环已经被很好地定义， 肺循环中的分子还不太清楚， 在吸入性LPS损伤中的具体作用尚未研究。 整体 这项研究的假设是，局部激活的血管 内皮细胞用于将中性粒细胞从肺毛细血管中移出 循环（和支气管毛细血管后小静脉）到空气空间 吸入内毒素后。 具体目标侧重于互动 中性粒细胞和内皮细胞以逐步的方式开始， 激活内皮细胞，然后激活中性粒细胞 整合素和牢固的粘附到内皮，并最终在 穿过内皮细胞层的迁移。 这个目标 调查是为了确定是否干预期间，每一个这些 中性粒细胞募集的阶段将有效地限制炎症 反应，并防止内毒素介导的病理生理后果 呼吸道疾病

DESCRIPTION (Taken from the Investigator's Abstract) The overall goal of this proposal includes a plan to foster the career development of Dr. Jessica Klekamp while understanding the investigation of a fundamental component of endotoxin mediated airway injury- neutrophil recruitment to the lung. Dr. Klekamp's long term career goal is to develop the education, research skills, and experience to become an independent physician-scientist capable of making a meaningful contribution in biomedical science. This award ,would allow her to fulfill her immediate goals of furthering her understanding of cellular interactions at the molecular level through course work, attaining new research skills in molecular biology, and continuing her investigation of leukocyte and endothelial cell adhesion molecules. This career development plan would take place in the ideal environment of the NIH-supported Specialized Center in Environmental Airway Disease, with Dr. David A. Schwartz as her mentor, the principal investigator for this specialized Center. This environment provides Dr. Klekamp both the resources and full access to the scientific expertise to make a significant contribution to the study of environmental lung disease. The proposed research project investigates the early pathogenic events that control movement of neutrophils from the vascular space to the airway, in an established murine model of endotoxin induced airway disease. While the role of leukocyte/endothelial cell adhesion molecules in neutrophil recruitment in the systemic circulation has been well defined, the involvement of these molecules in the pulmonary circulation is less well understood, and their specific role in inhaled LPS injury has not been studied. The overall hypothesis of this investigation is that a localized activated vascular endothelium serves to move the neutrophil from the pulmonary capillary circulation (and the bronchial post-capillary venules) to the airspace following inhalation of endotoxin. The specific aims focus on the interaction of the neutrophil and the endothelium in a stepwise fashion beginning with activation of the endothelium, followed by activation of the neutrophil integrins and firm adhesion to the endothelium, and culminating in transmigration across the endothelial cell layer. The goal of this investigation is to determine whether interventions during each of these phases of neutrophil recruitment will effectively limit the inflammatory response, and prevent the pathophysiologic consequences of endotoxin mediated airway disease.