ROLE OF ALVEOLAR MACROPHAGES IN LUNG INJURY AFTER TRAUMA

这项提议的长期目标是评估 活化的肺泡巨噬细胞(A-Mo)在肺泡巨噬细胞产生中的作用 肺损伤，通常使严重创伤后的恢复或 伯恩斯。在这种临床环境中，患者经常是败血症并伴有 伴发内毒素血症和/或持续较长时间的高 FI02通气机纠正低氧血症。内毒素(LPS)和氧气 已知的代谢物可以刺激钼，也与急性 肺损伤。A-Mo将被脂多糖和02中间体刺激 体内外和A-Mo产生促凝剂的能力 活性，2)细胞毒剂，3)成纤维细胞生长因子(S) 在体外和体内均得到证实。然后将尝试阻止 这些产品在体外，使用来自已知的三个组之一的药物 钼的调节功能：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，将在体外测试产生介体的抑制剂 活着。肺损伤的潜在改善将与 显微镜(光镜和电子显微镜)与肺血流动力学和呼吸 (利用慢性肺淋巴瘘)抑制剂之间的变化 经过处理的和未经处理的动物。因此，目标是确认 A-Mo产生有害介质与急性中毒的关系 肺损伤，并将这些产物的抑制与 从解剖学和生理学角度改善急性肺损伤 标准。

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.