Christensen T G, Breuer R, Hornstra L J, Lucey E C, Stone P J, Snider G L
Pulmonary Center, Boston University, School of Medicine, MA.
Exp Lung Res. 1987;13(3):279-97. doi: 10.3109/01902148709069594.
The central intrapulmonary bronchi of hamsters were examined by transmission electron microscopy at varying times following intratracheal instillation of human neutrophil elastase (HNE) or its vehicle, saline. Two hours after HNE treatment, there was a marked irregularity of the surfaces of many nonciliated epithelial cells; a differential count of transepithelial cells (those with both a basal lamina and luminal border) demonstrated a significant decrease in the proportion of granule-containing (granulated) secretory cells and a corresponding increase in nongranulated secretory cells. By 3 days after HNE injection, the differential count had returned to control levels and cell surface alterations were less evident. By 8 days, the proportion of granulated secretory cells had significantly increased, while that of nongranulated secretory cells had decreased. Many Clara cells developed the characteristics of mucous cells so that mucous cells constituted 57% of the secretory cells compared to 14% for the saline controls. The mucous cells contained an increased number of mucous granules including bizarre forms never seen in controls. By day 16, the average mucous cell proportion had increased to 75%; the mucous cells were larger and contained many more secretory granules than at day 8. At no time was there evidence of overt cell injury or alteration of extracellular connective tissue due to HNE. Basal and pseudobasal cells, distinguished by the presence or absence of hemidesmosomes, did not change as a percentage of total nucleated epithelial cells. Saline had no effect on the differential cell count compared to untreated values. Our results indicate a strong likelihood that HNE causes early discharge of secretory granules and alters the phenotypic expression of Clara cells so that they produce abundant, often abnormal mucous granules. The mechanism of HNE-induced disturbance of epithelial homeostasis is unknown, but the early irregularity of nonciliated epithelial cell surfaces may signify an important event in the evolution of the resultant lesion.
在仓鼠气管内注入人中性粒细胞弹性蛋白酶（HNE）或其溶剂生理盐水后，于不同时间通过透射电子显微镜检查仓鼠肺内中央支气管。HNE处理两小时后，许多无纤毛上皮细胞表面出现明显不规则；对跨上皮细胞（具有基底膜和管腔边界的细胞）进行差异计数显示，含颗粒（颗粒化）分泌细胞的比例显著下降，无颗粒分泌细胞的比例相应增加。HNE注射后3天，差异计数恢复到对照水平，细胞表面改变不太明显。到8天时，颗粒化分泌细胞的比例显著增加，而无颗粒分泌细胞的比例下降。许多克拉拉细胞呈现出黏液细胞的特征，使得黏液细胞占分泌细胞的57%，而生理盐水对照组为14%。黏液细胞中黏液颗粒数量增加，包括对照组中从未见过的奇异形态。到第16天，黏液细胞的平均比例增加到75%；与第8天相比，黏液细胞更大，含有更多的分泌颗粒。在任何时候都没有证据表明HNE导致明显的细胞损伤或细胞外结缔组织改变。通过半桥粒的存在与否区分的基底细胞和假基底细胞，占总核上皮细胞的百分比没有变化。与未处理的值相比，生理盐水对细胞差异计数没有影响。我们的结果表明，HNE极有可能导致分泌颗粒早期释放，并改变克拉拉细胞的表型表达，使其产生大量通常异常的黏液颗粒。HNE诱导上皮内稳态紊乱的机制尚不清楚，但无纤毛上皮细胞表面早期的不规则可能表明在最终病变演变过程中发生了一个重要事件。
