Christensen T G, Alonso P A
Mallory Institute of Pathology, Boston University School of Medicine, MA 02118, USA.
Eur Respir J. 1996 Mar;9(3):535-41. doi: 10.1183/09031936.96.09030535.
The bronchus is the only region of the hamster conducting airways to develop secretory cell metaplasia after an intratracheal instillation of human neutrophil elastase (HNE). We tested the hypothesis that this pathological change occurs because of cellular uptake of the enzyme that is specific to this region. HNE, dissolved in saline, was instilled into the trachea of hamsters, that were sacrificed 5, 15, 30 or 60 min later for immunocytochemical localization of the enzyme. Saline-treated animals served as controls. By light microscopy, HNE was evident only in the lumen and upon the epithelial surface in all airways, at all time points. Saline control tissues were negative. Electron microscopic immunogold staining revealed HNE within luminal macrophages and associated with mucus and, to a limited extent, upon the apical cell surface both in trachea and bronchus. A small amount of HNE staining occurred in the intercellular space and lamina propria of bronchi. Cytoplasmic gold particles were sparse both in treated and control animals. We conclude that instilled neutrophil elastase is excluded from the epithelial cytoplasm regardless of region. We thus reject the hypothesis of airway cellular uptake of HNE and suggest that stimulation of bronchial secretory cells to accumulate mucin granules is initiated at the cell surface, possibly by unmasking or altering region-specific receptors involved in signal transduction pathways governing mucin granule synthesis.
支气管是仓鼠气管中唯一在气管内注入人中性粒细胞弹性蛋白酶（HNE）后发生分泌细胞化生的区域。我们检验了这样一种假说，即这种病理变化的发生是由于该区域特异性的细胞对该酶的摄取。将溶解于生理盐水中的HNE注入仓鼠气管，5、15、30或60分钟后处死仓鼠，对该酶进行免疫细胞化学定位。用生理盐水处理的动物作为对照。通过光学显微镜观察，在所有时间点，所有气道的管腔和上皮表面均可见HNE。生理盐水对照组织呈阴性。电子显微镜免疫金染色显示，气管和支气管的管腔内巨噬细胞中有HNE，且与黏液相关，在一定程度上，HNE也存在于顶端细胞表面。支气管的细胞间隙和固有层有少量HNE染色。无论是处理组还是对照组动物，细胞质中的金颗粒都很少。我们得出结论，无论在哪个区域，注入的中性粒细胞弹性蛋白酶都不会进入上皮细胞质。因此，我们拒绝接受气道细胞摄取HNE的假说，并认为支气管分泌细胞积累黏蛋白颗粒的刺激是在细胞表面启动的，可能是通过暴露或改变参与调节黏蛋白颗粒合成的信号转导途径的区域特异性受体来实现的。
