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: 4693201
• 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/4693201
• 关键词: density gradient ultracentrifugation; diagnostic respiratory lavage; dosage; dust; environmental toxicology; extracellular; granule; lipid metabolism; lung alveolus; phospholipids; pulmonary surfactants; respiratory toxin; secretion; silicates

Pulmonary surfactant is synthesized and secreted by alveolar Type II cells. It is a complex mixture of lipids and proteins that prevents collapse of the alveoli and distal airways at low lung volumes. The pulmonary surfactant system is affected by numerous chemical and particulate toxicants through unknown mechanisms. Silica dust, when administered by either intratracheal injection or by inhalation, causes massive increases in the surfactant content of the lungs. The objectives of this work are to elucidate the mechanisms through which the pulmonary surfactant system is stimulated by silica and the processes responsible for the accumulation of phospholipids in the lungs. Twenty-eight days after a single intratracheal injection of silica into the lungs of rats (200mg/Kg) the phospholipid content of the lungs increased from 29.6 plus/minus 4.4 to 476.1 plus/minus 129.2 mg. Intracellular and extracellular surfactant pools accounted for 59.1 and 24.6% of this increase in phospholipids, respectively. These silica-induced increases in phospholipids of the intra- and extracellular surfactant pools were both dose- and time-dependent. Although the phospholipid content increased, the phospholipid composition of pulmonary surfactant did not change, in response to silica. Silica (10mg/Kg) increased surfactant phospholipid biosynthesis in the lungs of rats approximately 4-fold. Phospholipid fluxes between the intra- and extracellular pools increased from 115 Mug/hr to 437 Mug/hr. The turnover time for phospholipid in the intracellular pool was increased 3.5-fold from 13 hr to 45.4 hr but the turnover time for the extracellular pool increased only marginally from 10.4 hr to 13.9 hr. No evidence for recycling of surfactant was found. These data indicate that the expansion of the intra- and extracellular pools of surfactant phospholipids was due to increases in the biosynthesis of phospholipids and alterations in the kinetic relationship between the two pools.

肺表面活性物质由肺泡II型合成和分泌 细胞 它是脂质和蛋白质的复杂混合物， 肺泡和远端气道在低肺容量时塌陷。 的 肺表面活性物质系统受到许多化学物质的影响， 通过未知的机制产生的颗粒毒物。 硅尘，当 通过气管内注射或吸入给药， 肺部表面活性物质含量的大量增加 目标 这项工作的目的是阐明肺的机制， 表面活性剂系统受到二氧化硅的刺激， 肺中磷脂的积累。 28天后， 大鼠肺内单次注射二氧化硅（200 mg/Kg） 肺的磷脂含量从29.6 ± 4.4增加到 476.1 ± 129.2 mg。 细胞内外表面活性剂 混合物占磷脂增加的59.1%和24.6%， 分别 这些二氧化硅诱导的磷脂增加， 细胞内和细胞外表面活性剂池都是剂量-和 时间依赖性 虽然磷脂含量增加， 肺表面活性物质的磷脂组成没有改变， 对二氧化硅的反应 二氧化硅（10 mg/Kg）增加表面活性剂磷脂 在大鼠肺中的生物合成约为4倍。 磷脂 细胞内池和细胞外池之间的通量从115 μ g/hr 至437 μ g/hr。 合并液从13小时增加到45.4小时，增加了3.5倍，但 细胞外池从10.4小时到13.9小时仅略微增加。 没有发现表面活性剂回收的证据。这些数据表明 细胞内和细胞外的表面活性剂池的扩张 磷脂的增加是由于磷脂的生物合成增加， 两个池之间动力学关系的改变。