REGULATION OF PULMONARY SURFACTANT SYSTEM AND ITS MODIFICATION BY TOXIC AGENTS

肺表面活性物质是一种脂类和蛋白质的复杂混合物 在低肺容量时防止肺泡和远端气道塌陷。 许多化学和颗粒毒物，当吸入时，会影响 表面活性剂体系。由任一气管内注入的二氧化硅粉尘 注射或吸入会导致表面活性物质大量增加 肺的内容物。二氧化硅刺激细胞生长的机制 表面活性剂体系是未知的。肺表面活性物质系统包括 在两个主要的解剖结构不同的池中，一个细胞内池包含 在肺泡II型细胞和覆盖在其上的细胞外池内 肺泡上皮。这些水池似乎处于某种 共同监管，因为它们之间的关系似乎是 非常稳定。气管内注射二氧化硅粉尘可增加血浆中的 两个隔间中的表面活性物质含量不同，表明 这两个池子之间的比例可能会被有毒物质改变。 这些数据表明，在内部和外部空间之间存在大小关系 和胞外表面活性物质池，这种关系意味着 常见的调节机制，可能会受到肺损伤的干扰。这个 二氧化硅对表面活性体系的影响似乎是通过 肺泡II型细胞。这些细胞增加了2倍作为对 二氧化硅，此外，它们中的许多都增大了尺寸。我们已经隔离了 这些肥大的II型细胞和初步证据表明 染矽尘大鼠肺组织磷脂水平的升高 可能主要与这些高度活跃的 细胞。

Pulmonary surfactant is a complex mixture of lipids and proteins that prevents collapse of the alveoli and distal airways at low lung volumes. Numerous chemical and particulate toxicants, when inhaled, affect the surfactant system. Silica dust administered by either intratracheal injection or by inhalation, causes massive increases in the surfactant content of the lungs. The mechanisms through which silica stimulates the surfactant system are not known. The pulmonary surfactant system consists of two major anatomically distinct pools, an intracellular pool contained within the alveolar Type II cells and an extracellular pool that overlies the alveolar epithelium. These pools appear to be under some kind of common regulation because the relationship between them appears to be highly stable. Intratracheal injection of silica dust increased the levels of surfactant in both compartments but not to the same degree, indicating that the ratio between the two pools could be changed by toxic materials. These data suggest the existence of a size relationship between the intra- and extra-cellular pools of surfactant, a relationship that implies a common regulatory mechanism that can be disturbed by pulmonary injury. The effects of silica on the surfactant system appears to be mediated through the alveolar Type II cells. These cells increased 2-fold in response to silica and, in addition, many of them increased in size. We have isolated these hypertrophic Type II cells and preliminary evidence indicates that the increased levels of phospholipid in the lungs of silica-treated rats may be associated primarily with the appearance of these highly active cells.