BIOCHEMISTRY OF TRAUMA-INDUCED INFLAMMATION

白细胞蛋白水解酶和氧化剂在细胞周期中的作用 将检查组织炎性损伤的产生。 这些效应器的存在及其后果 在两个实验中，活动将与损伤的发生有关 炎症性疾病模型。这些是(1)体外培养， 灌流的兔肺，其中已知的氧化剂和蛋白酶，或 受刺激的人中性粒细胞将通过 血管系统，和(2)整个动物(兔子和恒河猴)， 在这种情况下，支气管内给予白细胞刺激会引起急性 和亚急性-慢性炎症。我们推测这些 模型基本上与创伤后出现的器官衰竭有关。 蛋白水解酶及其抑制物将在 用酶联免疫吸附试验(EL ISA法)进行活性和蛋白质的原位检测。氧化剂 将按照提案中的描述进行生化监测。 组织中蛋白水解酶和氧化剂靶标的改变 被评估，包括组织(细胞)的释放或分裂 纤维连接蛋白和层粘连蛋白进入可溶相，并断裂 细胞中DNA和NAD的耗竭，反映了暴露于 氧化剂。与慢性阻塞性肺疾病肺功能减退的关系 肺与炎症相关，肺表面活性物质的变化将 被分析。特别是，变化对 载脂蛋白将被定义。表面活性剂的更换将是 在实验模型中尝试确定其对 炎症性肺病中可见肺不张。

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.