REGULATION OF PULMONARY SURFACTANT SYSTEM AND ITS MODIFICATION BY TOXIC AGENTS

肺表面活性物质系统的调节及其有毒物质的修饰

• 批准号: 3876898
• 负责人: G R HOOK
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3876898
• 关键词: density gradient ultracentrifugation; diagnostic respiratory lavage; environmental toxicology; extracellular; laboratory rat; lipid metabolism; lung alveolus; phosphatidylcholines; phospholipids; protein biosynthesis; pulmonary surfactants; respiratory function; respiratory toxin; secretion; silicates; toxicant interaction

Pulmonary surfactant is a heterogeneous complex consisting of surface active phospholipids and specific proteins synthesized and secreted by Type II cells in the alveoli of the lungs. The major lipid component of surfactant is dipalmitoylphosphatidylcholine and the major protein component is surfactant protein A (SPA) . SPA is a specific surfactant-associated protein found only in the lungs. The function of DPPC is to lower surface tension at the air/cell interface and the function of SPA appears to be to assist in this process. Biosynthesis and secretion of these substances by alveolar Type II cells is critical for the stabiliza- tion and function of the lungs. Silica dust causes massive increases in the pulmonary content of both surfactant phospholipids and proteins. The induction of surfactant production in the lungs appears to be a result of the silica-induced inflammatory condition and the mechanism through which this occurs is currently under investigation. Some, but not all , Type II calls within the alveoli become hypertrophic and we have shown that these type II cells are in an activated state with regards to their ability to synthesize both surfactant phospholipids and SPA. These hypertrophic Type II cells are responsible for the massive increases in surfactant found in the lungs of silica-exposed rats. At the present time we are trying to determine the mechanism through which intratracheal injection of silica leads to activation of alveolar type II cells.

肺表面活性物质是一种多相复合物， 型合成和分泌的活性磷脂和特异性蛋白质 II细胞在肺泡。的主要脂质成分 表面活性剂是二棕榈酰磷脂酰胆碱， 表面活性剂蛋白A（SPA）。SPA是一种特殊的 仅在肺部发现的表面活性剂相关蛋白。DPPC的功能 降低空气/细胞界面的表面张力， SPA似乎有助于这一进程。生物合成和分泌 肺泡II型细胞的这些物质对于稳定 肺的功能和功能。 二氧化硅粉尘会导致肺内两种物质含量的大量增加， 表面活性剂磷脂和蛋白质。表面活性剂的诱导 肺中的产生似乎是二氧化硅诱导的结果。 炎症性疾病及其发生机制是 正在接受调查一些，但不是全部，第二类电话内， 肺泡变得肥大，我们已经证明这些II型细胞是 处于激活状态， 表面活性剂磷脂和SPA。这些肥大的II型细胞是 负责大量增加表面活性剂发现在肺部 暴露在二氧化硅中的老鼠目前，我们正在努力确定 通过该机制，硅胶的内注射导致 肺泡II型细胞的活化。