ROLE OF ALVEOLAR MACROPHAGES IN LUNG INJURY AFTER TRAUMA

本提案的长期目标是评估 “活化的”肺泡巨噬细胞（A-Mo）在产生 肺损伤，通常使严重创伤或 伯恩斯 在这种临床环境中，患者经常是脓毒症， 伴随内毒素血症和/或持续时间长， FI 02通气纠正低氧血症。 内毒素（LPS）和氧气 已知代谢物刺激Mo，并且还与急性 肺损伤 A-Mo将用LPS和02中间体刺激，两者均在 A-Mo在体外和体内产生：1）促凝血剂的能力 活性，2）细胞毒性剂，和3）成纤维细胞生长因子将被 在体外和体内证实。 然后将尝试阻止 这些产品在体外，利用来自已知的三组之一的试剂， 调节Mo功能：1）皮质类固醇，2）非类固醇 抗炎药（NSAID）和3）O2中间体的清除剂。 然后将在体外测试介质产生的抑制剂。 vivo. 肺损伤的潜在改善与以下因素相关： 显微镜（光和电子）和肺血流动力学和呼吸 抑制剂之间的变化（利用慢性肺淋巴瘘） 预处理和未处理的动物。 因此，目标是确认 A-Mo和急性毒性介质产生的关系 肺损伤，以及这些产物的抑制与 从解剖和生理两方面改善急性肺损伤 的搜索.

The long term objective of this proposal is to evaluate the potential contribution of the "activated" alveolar macrophage (A-Mo) in producing the lung injury that commonly complicates recovery from severe trauma or burns. In this clinical setting, the patients are frequently septic with a concomitant endotoxemia and/or sustained for prolonged periods with high FI02 ventilation to correct hypoxemia. Both endotoxin (LPS) and oxygen metabolites are known to stimulate Mo and are also associated with acute lung injury. A-Mo will be stimulated with LPS and 02 intermediates both in vitro and in vivo and the ability of A-Mo to produce: 1) procoagulant activity, 2) cytotoxic agents, and 3) fibroblast growth factor(s) will be confirmed in vitro and the in vivo. Attempts will then be made to block these products in vitro, utilizing agents from one of three groups known to modulate Mo functions: 1) corticosteroids, 2) non-steroidal anti-inflammatory drugs (NSAID) and 3) scavengers of O2 intermediates. The inhibitors of mediator production in vitro will then be tested in vivo. Potential amelioration of lung injury will be correlated with microscopic (light and electron) and pulmonary hemodynamic and respiratory changes (utilizing a chronic lung lymph fistula) between inhibitor pretreated and untreated animals. The goal is thus to confirm the association of the production of deleterious mediators by A-Mo and acute lung injury, and correlate inhibition of these products with an amelioration of the acute lung injury by both anatomic and physiologic criteria.