BIOCHEMISTRY OF TRAUMA-INDUCED INFLAMMATION

1.兔和恒河猴炎症模型研究表明 静脉注射细菌脂多糖的刺激作用 途径诱导白细胞在管腔表面聚集 肺血管，不移行到血管外和 牙槽间隙，无明显组织损伤。相反， 脂多糖支气管内刺激诱导白细胞迁徙和 损伤，并与肿瘤坏死因子、白介素1、白介素8和白介素6的产生有关 肺部。治疗后肺组织中未发现这些细胞因子 内毒素静脉刺激。我们建议确定抑制是否 这些细胞因子改变了细胞因子的顺序出现， 肺内白细胞移行和病理生理改变。这个 IL-8的受体结合域已初步确定，并 这一领域的抗体将被用来评估 IL-8在内毒素诱导的白细胞游走中的作用 肝脏IL-6胞外亲水区的结构域 受体，负责结合信号转导组件， GP-130将被鉴定，并准备针对它的抗体。这些 将使用抗体来阻断急性期肝细胞中的IL-6 蛋白质，脂多糖结合蛋白(LBP)。LBP可能会参与 兔对脂多糖表现出的高反应状态 在24小时内发展。抑制IL-6受体可能 不仅要改变LBP的形成，而且要改变超反应状态。 2.将继续进行关于白细胞氧化剂在 炎症性损伤。到目前为止的研究已经定义了在 暴露在白细胞氧化剂中的细胞将显著有助于 研究了氧化剂的缓蚀效果。

1. Models of inflammation in rabbits and rhesus monkeys have indicated that stimulation by bacterial lipopolysaccharide (LPS) by the intravenous route induces accumulation of leukocytes on the luminal surface of pulmonary blood vessel, without emigration into the extravascular and alveolar spaces and without demonstrable tissue injury. By contrast, intrabronchial stimulation with LPS induces emigration of leukocytes and damage, and is associated with generation of TNF, IL-1, IL-8 and IL-6 in the lung. These cytokines are not found in the lung tissues after intravenous stimulation with LPS. We propose to determine if inhibition of these cytokines modifies the sequential appearance of cytokines, leukocytic emigration and pathophysiologic changes in the lung. The receptor-binding domain of IL-8 has been tentatively identified, and antibodies to this domain will be employed to assess the importance of IL-8 in LPS-induced leukocytic emigration. The domain of the extracellular hydrophilic region of the hepatic IL-6 receptor, responsible for binding the signal-transducing component, GP-130, will be identified, and antibodies prepared to it. These antibodies will be used to block IL-6 in hepatocytes of the acute phase protein, LPS-binding protein (LBP). LBP may participate in the appearance of the hyper-responsive state exhibited by rabbits to LPS that develops over a 24 hour period. Inhibition of the IL-6 receptor may modify not only LBP formation, but the hyper-responsive state. 2. Experiments will be continued on the role of leukocytic oxidants in inflammatory injury. Studies to date have defined specific changes in cells exposed to leukocytic oxidants that will help significantly in studying the effect of oxidant inhibition.