GRANULOCYTE EMIGRATION AND SEPTIC LUNG INJURY

本课题旨在探讨实验性脓毒症肺的发生机制 损伤，特别强调嗜神经细胞（PMN）的贡献 粘附于内皮细胞。 实验性肺损伤被用作 美国成人呼吸窘迫综合征模型， 首次报道时死亡率超过50% 死亡率 在过去的20年里保持不变。 PMNs及其产品 肺泡灌洗液是ARDS的标志， 造成实验性肺损伤第一个具体目标将 广泛表征与三种已知的 肺损伤的原因。 用于产生伤害的协议具有其 发生在创伤受害者身上的事件。 在具体目标2和3中， 将用单克隆抗体（MAb）60.3以不同的浓度处理兔。 制定的议定书的具体目标是1。 MAb 60.3是 针对CD 11/CD 18糖蛋白粘附上的功能表位 复合物并阻断CD 18依赖性PMN粘附。 的 该建议假设预测PMNs负责肺 脓毒症模型中的损伤。 此外，他们预测PMNs形成一个 保护微环境，阻止环境的形成， 抗CD 18单克隆抗体将显著减轻损伤。 抗CD 18单克隆抗体治疗可有效预防肺损伤 由于CD 18似乎是肺粘附的主要机制， 对活E.大肠杆菌细菌或大肠杆菌内毒素。

This project will investigate the mechanism of experimental septic lung injury with particular emphasis on the contribution of neurophil (PMN) adherence to endothelial cells. Experimental lung injury is used as a model of the adult respiratory distress syndrome in the United States with a mortality greater than 50% when it was first reported. Mortality had remained unchanged over the past 20 years. PMNs and their products in alveolar lavage fluid are hallmarks of ARDS and they have been implicated in causing experimental lung injury. The first specific aim will extensively characterize physiologic changes associated with three known cause of lung injury. The protocol used to produce injury have their origin in events that occur in trauma victims. In specific aims 2 and 3, rabbits will be treated with the monoclonal antibody (MAb) 60.3 at various times int he protocol developed is specific aim 1. The MAb 60.3 is directed to a functional epitope on the CD11/CD18 glycoprotein adherence complex on the PMNs and blocks CD18 dependent PMN adherence. The hypothesis of this proposal predict that PMNs are responsible for lung injury in models of sepsis. Further, they predict that PMNs form a protected microenvironment and blocking formation of that environment with anti-CD18 monoclonal antibodies will significantly reduce the injury. Treatment with ant-CD18 MAb will be effective in preventing lung injury since CD18 appeared to be in major mechanism of adherence in lung in response to live E. coli bacteria or E.coli endotoxin.