INFLAMMATORY INJURY OF LUNG ALVEOLAR EPITHELIAL CELLS

成人呼吸窘迫时的肺泡损伤 综合征(ARDS)在许多情况下似乎是继发性的 激活炎症过程，特别是涉及 中性粒细胞和/或氧气代谢物。肺泡损伤 上皮细胞已被发现是一种突出的早期特征。 阿兹。因为肺泡上皮的完整性是至关重要的 在防止液体积聚在肺泡内 因为肺泡上皮细胞已经接受了 与血管内皮细胞相比，这方面的研究相对较少 提案包含了为研究这些机制而设计的实验。 刺激的中性粒细胞和/或氧代谢物可以 损伤肺上皮细胞。假设是：胡言乱语 在三磷酸腺苷的代谢过程中密切相关 损伤；靶细胞对中性粒细胞诱导的敏感性 损伤取决于它们解毒氧化剂的能力；以及 上皮细胞膜损伤是一个突出的早期特征 中性粒细胞引起的损伤。为了检验这些假设，我们将 暴露培养的大鼠肺泡上皮细胞。(及 牛肺动脉内皮细胞)与 刺激的人中性粒细胞和/或外源性氧气 代谢物。我们将同时测量细胞毒性， 三磷酸腺苷及相关化合物的浓度、活性 细胞内抗氧化系统和特异膜 功能。这些信息将被用来构建详细的 氧代谢产物和刺激的中性粒细胞的途径 损伤肺泡上皮细胞。所获得的信息 将提供对炎性损伤的更好的理解 至肺泡上皮细胞，并应协助开发治疗方法 旨在减少急性呼吸窘迫综合征的肺损伤。

The alveolar injury that occurs in the adult respiratory distress syndrome (ARDS) appears in many cases to be secondary to activation of inflammatory processes, particularly those involving neutrophils and/or oxygen metabolites. Injury of alveolar epithelial cells has been found to be a prominent, early feature of ARDS. Because the integrity of the alveolar epithelium is critical in preventing fluid from accumulating within the alveolar compartment, and because the alveolar epithelium has received relatively little study compared to the vascular endothelium, this proposal contains experiments designed to study the mechanisms by which stimulated neutrophils and/or oxygen metabolites can injure lung epithelial cells. The hypotheses are: that abberations in ATP metabolism are intimately involved in the process of injury; that the susceptibility of target cells to neutrophil-induced injury is dependent upon their ability to detoxify oxidants; and that epithelial cell membrane injury is a prominent, early feature of neutrophil-induced injury. to test these hypotheses, we will expose cultured rat pulmonary alveolar epithelial cells. (and for comparison bovine pulmonary artery endothelial cells) to stimulated human neutrophils and/or exogenous oxygen metabolites. We will concurrently measure cytotoxicity, concentrations of ATP and related compounds, the activities of intracellular antioxidant systems, and specific membrane functions. The information will be used to construct a detailed pathway be which oxygen metabolites and stimulated neutrophils injure pulmonary alveolar epithelial cells. The information gained will provide an improved understanding of inflammatory damage to alveolar epithelium and should assist in developing treatments designed to reduce the lung injury in ARDS.