Massion P P, Inoue H, Richman-Eisenstat J, Grunberger D, Jorens P G, Housset B, Pittet J F, Wiener-Kronish J P, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
J Clin Invest. 1994 Jan;93(1):26-32. doi: 10.1172/JCI116954.
Because high concentrations of IL-8 are found in the sputum of cystic fibrosis patients, we hypothesized that Pseudomonas aeruginosa (PA) induces the production of IL-8 in airway epithelial cells and in monocytes. Therefore, we incubated the supernatant from PA culture with human transformed bronchial epithelial cells (16-HBE) or with monocytes. The culture medium of 16-HBE cells that had been incubated with PA supernatant for 6 h had chemotactic activity that was inhibited by an antibody to human IL-8. The PA supernatant induced IL-8 production by primary bronchial epithelial cells, by 16-HBE cells, and by monocytes. After incubation with PA supernatant, 16-HBE cells showed a marked increase in the levels of IL-8 gene expression. The PA product responsible for IL-8 production resisted freezing, boiling, and proteolysis. This product was not lipid extractable and was present in a 1-kD filtrate. We conclude that a small molecular mass product of PA stimulates IL-8 production by 16-HBE cells and by monocytes, and that the chemotactic activity produced by 16-HBE cells after exposure to PA is due principally to IL-8.
由于在囊性纤维化患者的痰液中发现了高浓度的白细胞介素-8(IL-8),我们推测铜绿假单胞菌(PA)可诱导气道上皮细胞和单核细胞产生IL-8。因此,我们将PA培养物的上清液与人转化支气管上皮细胞(16-HBE)或单核细胞一起孵育。与PA上清液孵育6小时的16-HBE细胞的培养基具有趋化活性,该活性可被抗人IL-8抗体抑制。PA上清液可诱导原代支气管上皮细胞、16-HBE细胞和单核细胞产生IL-8。与PA上清液孵育后,16-HBE细胞中IL-8基因表达水平显著增加。负责产生IL-8的PA产物能抵抗冷冻、煮沸和蛋白水解。该产物不能用脂质提取,且存在于1-kD的滤液中。我们得出结论,PA的一种小分子质量产物可刺激16-HBE细胞和单核细胞产生IL-8,并且16-HBE细胞在暴露于PA后产生的趋化活性主要归因于IL-8。