GRANULOCYTE EMIGRATION AND SEPTIC LUNG INJURY

本课题将对实验性败血症肺的发病机制进行研究。 损伤，特别强调嗜神经细胞(PMN)的作用 黏附于内皮细胞。实验性肺损伤被用作 美国成人呼吸窘迫综合征模型 首次报告时的死亡率超过50%。死亡率有 在过去的20年里保持不变。中国的PMN及其产品 肺泡灌洗液是ARDS的特征，它们被认为与ARDS有关 导致实验性肺损伤。第一个具体目标是 广泛描述与三个已知因素有关的生理变化 肺损伤的原因。用于造成伤害的方案有它们的 起源于发生在创伤受害者身上的事件。在具体目标2和3中， 用单抗(MAb)60.3处理不同剂量的兔。 制定的协议的具体目标是1。MAB 60.3是 针对CD11/CD18糖蛋白黏附的功能表位 PMN上的复合体，并阻断CD18依赖的PMN的黏附。这个 这一假说预测中性粒细胞与肺有关。 脓毒症模型中的损伤。此外，他们预测PMN形成了一种 保护微环境并阻止该环境的形成 抗CD18单抗将明显减轻损伤。 ANT-CD18单抗治疗可有效预防肺损伤 由于CD18似乎是肺组织黏附的主要机制 对活的大肠杆菌或大肠杆菌内毒素的反应。

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.