Ito Nobuko, Hirota Keiko, Momoeda Kanako, Iwamori Masao
Department of Anesthesiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Transl Res. 2006 Aug;148(2):96-102. doi: 10.1016/j.trsl.2006.04.001.
Cholesterol sulfate (CS) in the gastrointestinal tract exhibits a mucosal protective activity in mouse ulcer model. To clarify the possible role of CS for protection from the epithelial injury due to neutrophil elastase in the tracheobronchi, the authors determined the concentrations of CS and neutrophil elastase in bronchoalveolar lavage fluid (BALF) from patients under anesthesia, and they examined the inhibitory activity of CS toward neutrophil elastase. The concentrations of CS and neutrophil elastase were determined by thin-layer chromatography and enzyme-linked immunosorbent assaying, respectively, and the effect of CS on the activity of elastase was determined with a chromogenic substrate. CS was found to be present in human lung, tracheal mucosa, and BALF, and a high synthesis of it was detected in the tracheal mucosa, in which cellular cholesterol sulfotransferase was induced depending on the density of tracheal cells. Among lipids in the tracheal mucosa, only CS was demonstrated to exhibit inhibitory activity toward neutrophil elastase, a powerful erosive agent in inflammation. The secretion of elastase from neutrophils into BALF was stimulated during the course of general anesthesia. In contrast, the amount of CS in BALF gradually decreased during anesthesia. On immune-precipitation of neutrophil elastase in BALF, CS was detected in the immune precipitate, which indicates a possible association of CS with neutrophil elastase in BALF.
CS, which is a major acidic lipid in the tracheobronchial epithelium, might function as an epithelial inhibitor toward neutrophil elastase secreted in response to several stimuli such as anesthesia.
胆固醇硫酸酯(CS)在胃肠道中对小鼠溃疡模型具有黏膜保护活性。为阐明CS在保护气管支气管免受中性粒细胞弹性蛋白酶所致上皮损伤方面的可能作用,作者测定了麻醉患者支气管肺泡灌洗液(BALF)中CS和中性粒细胞弹性蛋白酶的浓度,并检测了CS对中性粒细胞弹性蛋白酶的抑制活性。分别采用薄层色谱法和酶联免疫吸附测定法测定CS和中性粒细胞弹性蛋白酶的浓度,并用显色底物测定CS对弹性蛋白酶活性的影响。发现CS存在于人类肺组织、气管黏膜和BALF中,在气管黏膜中检测到其高合成,其中细胞胆固醇硫酸转移酶根据气管细胞密度诱导产生。在气管黏膜的脂质中,只有CS对中性粒细胞弹性蛋白酶(炎症中一种强大的侵蚀剂)表现出抑制活性。在全身麻醉过程中,中性粒细胞向BALF分泌弹性蛋白酶受到刺激。相反,麻醉期间BALF中CS的量逐渐减少。对BALF中的中性粒细胞弹性蛋白酶进行免疫沉淀时,在免疫沉淀物中检测到CS,这表明CS可能与BALF中的中性粒细胞弹性蛋白酶有关。
CS是气管支气管上皮中的主要酸性脂质,可能作为一种上皮抑制剂,对抗因麻醉等多种刺激而分泌的中性粒细胞弹性蛋白酶。