INFLAMMATORY INJURY OF LUNG ALVEOLAR EPITHELIAL CELLS

肺泡上皮细胞炎症损伤

• 批准号: 3356735
• 负责人: Richard H Simon
• 金额: $ 12.46万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-07-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3356735
• 关键词: adult respiratory distress syndrome; calcium transporting ATPase; cell adhesion; cell death; cell membrane; cellular pathology; cow; cytotoxicity; detoxification; electron microscopy; fluorescent dye /probe; high performance liquid chromatography; human tissue; hydrogen peroxide; inflammation; laboratory rat; lung alveolus; membrane permeability; monoclonal antibody; neutrophil; nucleotide metabolism; oxidizing agents; oxidoreductase; respiratory epithelium; scanning electron microscopy; singlet oxygen; tissue /cell culture; vascular endothelium

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.

成人呼吸窘迫时发生的肺泡损伤 急性呼吸窘迫综合征（ARDS）在许多情况下似乎是继发于 炎症过程的激活，特别是那些涉及 中性粒细胞和/或氧代谢物。 肺泡损伤 上皮细胞被发现是一个突出的，早期的特征， ARDS。 因为肺泡上皮的完整性至关重要 防止液体在肺泡内积聚 由于肺泡上皮细胞已经接受了 与血管内皮相比，研究相对较少， 建议包含旨在研究机制的实验 刺激的嗜中性粒细胞和/或氧代谢物可以 损伤肺上皮细胞。 假设是：变异 在ATP代谢的过程中， 损伤;靶细胞对嗜铬细胞瘤诱导的 损伤取决于它们对氧化剂解毒的能力; 上皮细胞膜损伤是一个突出的早期特征， 造成的伤害 为了验证这些假设，我们将 培养大鼠肺泡上皮细胞。(and为 比较牛肺动脉内皮细胞）与 刺激的人中性粒细胞和/或外源性氧 代谢物。 我们将同时测量细胞毒性， ATP和相关化合物的浓度， 细胞内抗氧化系统和特定膜 功能协调发展的 这些信息将用于构建详细的 氧代谢途径和刺激的中性粒细胞 损伤肺泡上皮细胞。 获得的信息 将有助于我们更好地了解炎症损伤 应该有助于开发治疗方法 旨在减少ARDS中的肺损伤。