BIOCHEMISTRY OF TRAUMA-INDUCED INFLAMMATION

白细胞蛋白酶和氧化剂参与了 检查组织炎性损伤的产生。 这些效应物的存在及其后果 活动将与两个实验中的损伤发展相关 炎症性疾病的模型。 这些是（1）体外， 灌注的兔肺，其中已知的氧化剂和蛋白酶，或 刺激的人中性粒细胞将通过 脉管系统，和（2）整个动物（兔和恒河猴）， 其中支气管内给予白细胞刺激诱导急性 和亚急性-慢性炎症。 我们假设这些 模型基本上与创伤后出现的器官衰竭有关。 蛋白酶及其抑制剂将在 通过活性和蛋白质测定（ELISA方法）原位测定。 氧化剂 将按照提案中所述进行生化监测。 组织中蛋白酶和氧化剂靶点的改变， 评估，包括组织（细胞）的释放或裂解 纤连蛋白和层粘连蛋白进入可溶相，并发生链断裂 细胞中的DNA和NAD的消耗，反映了暴露于 氧化剂 与肺功能减退的关系 与炎症相关的肺，表面活性物质的改变将 被分析。 特别是， 将定义脱辅基蛋白。 表面活性剂的替代将是 试图在实验模型中确定其对 在炎性肺病中观察到肺不张。

The participation of leukocytic proteases and oxidants in the production of inflammatory injury of tissues will be examined. The presence of these effectors and the consequences of their activity will be related to injury developing in two experimental models of inflammatory disease. These are (1) the in vitro, perfused rabbit lung, in which known oxidants and proteases, or stimulated human neutrophils will be perfused through the vasculature, and (2) whole animals (rabbits and rhesus monkeys), in which leukocytic stimuli given intrabronchially induce acute and subacute-chronic inflammation. We presume that these models relate basically to the organ failure seen after trauma. Proteases and their inhibitors will be quantitatively measured in situ by assays of activity and protein (ELISA methods). Oxidants will be monitored biochemically as described in the proposal. Alterations of targets of protease and oxidants in the tissues will be assessed, including release or cleavage of tissue (cellular) fibronectin and laminin into the soluble phase, and strand breaks of DNA and depletion of NAD in cells, reflecting exposure to oxidants. In relationship to diminished pulmonary function of the lung associated with inflammation, alterations in surfactant will be analyzed. In particular, the effect of changes in the apoprotein will be defined. Replacement of surfactant will be attempted in experimental models to determine its effect on the atelectasis observed in inflammatory lung disease.