Miller B E, Hook G E
Laboratory of Pulmonary Pathobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Biochem J. 1988 Aug 1;253(3):659-65. doi: 10.1042/bj2530659.
The effects of intratracheally instilled silica (10 mg/rat) on the biosynthesis of surfactant phospholipids was investigated in the lungs of rats. The sizes of the intracellular and extracellular pools of surfactant phospholipids were measured 7, 14 and 28 days after silica exposure. The ability of lung slices to incorporate [14C]choline and [3H]palmitate into surfactant phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) was also investigated. Both intra- and extra-cellular pools of surfactant phospholipids were increased by silica treatment. The intracellular pool increased linearly over the 28-day time period, ultimately reaching a size 62-fold greater than controls. The extracellular pool also increased, but showed a pattern different from that of the intracellular pool. The extracellular pool increased non-linearly up to 14 days, and then declined. At its maximum, the extracellular pool was increased 16-fold over the control. The ability of lung slices to incorporate phospholipid precursors into surfactant-associated PC and DSPC was elevated at all time periods. The rate of incorporation of [14C]choline into surfactant PC and DSPC was maximal at 14 days and was nearly 3-fold greater than the rate in controls. The rate of incorporation of [3H]palmitate was also maximal at 14 days, approx. 5-fold above controls for PC and 3-fold for DSPC. At this same time point, the microsomal activity of cholinephosphate cytidylyltransferase was increased 4.5-fold above controls, but cytosolic activity was not significantly affected by silica treatment. These data indicate that biosynthesis of surfactant PC is elevated after treatment of lungs with silica and that this increased biosynthesis probably underlies the expansion of the intra- and extra-cellular pools of surfactant phospholipids.
研究了气管内注入二氧化硅（10毫克/只大鼠）对大鼠肺表面活性物质磷脂生物合成的影响。在二氧化硅暴露后7天、14天和28天测量了表面活性物质磷脂的细胞内和细胞外池大小。还研究了肺切片将[14C]胆碱和[3H]棕榈酸酯掺入表面活性物质磷脂酰胆碱（PC）和二饱和磷脂酰胆碱（DSPC）的能力。二氧化硅处理使表面活性物质磷脂的细胞内和细胞外池均增加。细胞内池在28天的时间段内呈线性增加，最终达到比对照组大62倍的大小。细胞外池也增加了，但呈现出与细胞内池不同的模式。细胞外池在14天内非线性增加，然后下降。在其最大值时，细胞外池比对照组增加了16倍。在所有时间段，肺切片将磷脂前体掺入与表面活性物质相关的PC和DSPC的能力均升高。[14C]胆碱掺入表面活性物质PC和DSPC的速率在14天时最大，几乎是对照组速率的3倍。[3H]棕榈酸酯的掺入速率在14天时也最大，PC约为对照组的5倍，DSPC约为对照组的3倍。在同一时间点，胆碱磷酸胞苷转移酶的微粒体活性比对照组增加了4.5倍，但胞质活性未受到二氧化硅处理的显著影响。这些数据表明，用二氧化硅处理肺后，表面活性物质PC的生物合成增加，这种增加的生物合成可能是表面活性物质磷脂细胞内和细胞外池扩大的基础。
