Marchand V, Tournier J M, Polette M, Nawrocki B, Fuchey C, Pierrot D, Burlet H, Puchelle E
INSERM Unité 314, Université de Reims, C.H.R. Maison Blanche, France.
Eur J Pharmacol. 1997 Oct 8;336(2-3):187-96. doi: 10.1016/s0014-2999(97)01222-3.
During airway inflammation, proteinases such as human leukocyte elastase are actively secreted. Secretory leukocyte protease inhibitor is a major serine proteinase inhibitor, secreted by bronchial, bronchiolar and lung epithelial cells. We recently identified secretory leukocyte protease inhibitor in human nasal epithelium, exclusively in remodelled areas of the surface epithelium. We now investigated the influence of remodelling and inflammation of the nasal tissue on the in vitro capacity of these cells to respond to human leukocyte elastase. Primary cultures of surface epithelial cells were established from various nasal polyp samples. At confluency, cell cultures were exposed to different human leukocyte elastase concentrations. The secretory leukocyte protease inhibitor immunocytolocalisation, expression and secretion were then investigated. Immunocytochemistry, showed a human leukocyte elastase dose-dependent increase of secretory leukocyte protease inhibitor containing cells and a basal extracellular localization of secretory leukocyte protease inhibitor after incubation with 100 microg/ml human leukocyte elastase. The relative amount of secretory leukocyte protease inhibitor mRNA transcripts increased with respect to the human leukocyte elastase concentration. Nevertheless, the potential stimulation of secretory leukocyte protease inhibitor secretion by human leukocyte elastase was lower in the more remodelled and inflamed tissue. Our results suggest that the contribution of the surface epithelial cells of poorly remodelled tissues to the protection against the deleterious effect of neutrophil proteinases is severely decreased in highly remodelled and inflamed tissues.
在气道炎症期间，诸如人白细胞弹性蛋白酶之类的蛋白酶会被大量分泌。分泌型白细胞蛋白酶抑制剂是一种主要的丝氨酸蛋白酶抑制剂，由支气管、细支气管和肺上皮细胞分泌。我们最近在人鼻上皮中发现了分泌型白细胞蛋白酶抑制剂，且仅存在于表面上皮的重塑区域。我们现在研究鼻组织的重塑和炎症对这些细胞体外响应人白细胞弹性蛋白酶能力的影响。从各种鼻息肉样本中建立表面上皮细胞的原代培养物。在细胞汇合时，将细胞培养物暴露于不同浓度的人白细胞弹性蛋白酶中。然后研究分泌型白细胞蛋白酶抑制剂的免疫细胞定位、表达和分泌情况。免疫细胞化学显示，在与100微克/毫升人白细胞弹性蛋白酶孵育后，含分泌型白细胞蛋白酶抑制剂的细胞呈人白细胞弹性蛋白酶剂量依赖性增加，且分泌型白细胞蛋白酶抑制剂在细胞外呈基础定位。分泌型白细胞蛋白酶抑制剂mRNA转录本的相对量随人白细胞弹性蛋白酶浓度的增加而增加。然而，在重塑和炎症程度更高的组织中，人白细胞弹性蛋白酶对分泌型白细胞蛋白酶抑制剂分泌的潜在刺激作用较低。我们的结果表明，在高度重塑和发炎的组织中，重塑程度低的组织表面上皮细胞对抵御中性粒细胞蛋白酶有害作用的贡献会严重降低。
