REGULATION OF PULMONARY SURFACTANT SYSTEM AND ITS MODIFICATION BY TOXIC AGENTS

肺表面活性物质是脂质和蛋白质的复杂混合物 防止肺泡和远端气道在低通气时塌陷， 肺容量 二氧化硅粉尘导致大量增加， 肺表面活性物质含量，但通过其机制， 这种情况的发生是未知的。 审查在某些情况下， 合成、分泌和清除表面活性剂磷脂 从二氧化硅处理的大鼠的肺中发现， 表面活性剂的细胞内和细胞外池可以被计算 因为表面活性剂 磷脂由肺泡II型细胞合成，分泌， 然后从肺泡中清除 一般情况下 这些合成、分泌和清除的速率是相同的 并且细胞内和细胞外的表面活性剂池不改变 在尺寸上。 我们的研究表明， 表面活性剂池是生物合成速率的改变， 合成表面活性剂磷脂， 生物合成率主要与亚种群有关 II型细胞的高度活化， 合成表面活性剂磷脂的能力。 我们已经开发 一种用于分离这些活化的II型细胞的方法， 二氧化硅处理的大鼠的肺， 活化的细胞与非活化的或正常的II型细胞。 检查磷脂酰胆碱是通过什么途径， 合成表明，增加的合成是通过显着的 两种酶的活性升高;胞苷酰转移酶 和胆碱磷酸转移酶。 表面活性剂的活化 二氧化硅的途径可能通过这两个关键途径介导 磷脂酰胆碱生物合成途径中的酶。 在 此外，这些活化的II型细胞似乎 在肺泡内的修复过程中发挥作用， 肺 初步证据表明，过度活跃的II型 细胞也是肺泡内的增殖细胞。 未来 研究将涉及进一步的特征， II型细胞及其在修复过程中作用的研究- 在肺部。

Pulmonary surfactant is a complex mixture of lipids and proteins that prevents collapse of the alveoli and distal airways at low lung volumes. Silica dust causes massive increases in the surfactant content of the lungs but the mechanisms through which this occurs are not known. Examination of the rates at which surfactant phospholipids are synthesized, secreted, and cleared from the lungs of silica-treated rats revealed that expansion of the intra and extracellular pools of surfactant could be accounted for by imbalances between the rates at which surfactant phospholipids are synthesized by alveolar Type II cells, secreted, and then cleared from the alveoli. Under normal circumstances these rates of synthesis, secretion, and clearance are the same and the intra- and extra-cellular pools of surfactant do not change in size. Our studies indicate that central to the expansion of surfactant pools are alterations in the biosynthetic rates at which surfactant phospholipids are synthesized and that these increased biosynthetic rates are associated primarily with a subpopulation of Type II cells that are highly activated with regard to their ability to synthesize surfactant phospholipids. We have developed a method for the isolation of these activated Type II cells from the lungs of silica-treated rats and for the separation of those activated cells from the non-activated or normal Type II cells. Examination of the pathway by which phosphatidylcholine is synthesized reveals that increased synthesis is achieved by marked elevation in the activities of two enzymes; cytidylyltransferase and choline phosphotransferase. Activation of the surfactant pathway by silica may be mediated through these two critical enzymes in the biosynthetic pathway of phosphatidylcholine. In addition, it appears likely that these activated Type II cells play a role in the repair processes within the alveoli of the lungs. Preliminary evidence indicates that hyperactive Type II cells are also the proliferative cells within the alveoli. Future studies will involve further characterization of the hyperactive Type II cells and investigation of their role in repair processes- within the lungs.