Abdelaziz M M, Devalia J L, Khair O A, Rusznak C, Calderon M, Sapsford R J, Bayram H, Davies R J
Academic Dept of Respiratory Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, The London Chest Hospital, UK.
Eur Respir J. 1997 Apr;10(4):851-7.
Although some studies have shown that long-term treatment of asthmatics with nedocromil sodium can reduce airway hyperresponsiveness and improve symptoms and lung function, the mechanisms underlying its effects are not well understood. We have investigated the effect of nedocromil sodium on eosinophil chemotaxis, eosinophil adherence to human endothelial cells and release of soluble intercellular adhesion molecule-1 (sICAM-1) from endothelial cells, induced by conditioned medium collected from cultured human bronchial epithelial cells. Conditioned medium significantly increased eosinophil chemotaxis from a baseline median value of 2.1 (range 1.9-4.5) cells-high power field(-1) (HPF) to 10.5 (range 7.8-12.3) cells-HPF(-1) (p<0.05). Similarly, conditioned medium significantly increased eosinophil adherence to endothelial cells from a baseline value of 9 (range 8-12)% to 23 (range 21-30)% (p<0.05). Nedocromil sodium, at 10(-5) M concentration, significantly attenuated the eosinophil chemotaxis and adherence induced by conditioned medium. Conditioned medium also significantly increased the release of sICAM-1 from endothelial cells, from a baseline value of 11.5 (range 8.1-15.4) pg x microg(-1) protein to 67.6 (range 55.6-73.5) pg x microg(-1) protein (p<0.05). This was significantly attenuated by anti-tumour necrosis factor-alpha (TNF-alpha), anti-interleukin-1beta (IL-1beta) and 10(-5) M nedocromil sodium. These findings suggest that human bronchial epithelial cell-derived mediators may potentiate eosinophil activity, and that this can be modulated by nedocromil sodium, suggesting a possible mechanism underlying its anti-inflammatory effect.
尽管一些研究表明，用奈多罗米钠对哮喘患者进行长期治疗可降低气道高反应性、改善症状和肺功能，但其作用机制尚未完全明确。我们研究了奈多罗米钠对嗜酸性粒细胞趋化性、嗜酸性粒细胞与人内皮细胞的黏附以及内皮细胞释放可溶性细胞间黏附分子-1（sICAM-1）的影响，这些影响是由从培养的人支气管上皮细胞收集的条件培养基诱导产生的。条件培养基使嗜酸性粒细胞趋化性从基线中位数2.1（范围1.9 - 4.5）个细胞/高倍视野（-1）（HPF）显著增加至10.5（范围7.8 - 12.3）个细胞/HPF（-1）（p<0.05）。同样，条件培养基使嗜酸性粒细胞与内皮细胞的黏附从基线值9（范围8 - 12）%显著增加至23（范围21 - 30）%（p<0.05）。浓度为10（-5）M的奈多罗米钠显著减弱了条件培养基诱导的嗜酸性粒细胞趋化性和黏附。条件培养基还使内皮细胞sICAM-1的释放从基线值11.5（范围8.1 - 15.4）pg x μg（-1）蛋白显著增加至67.6（范围55.6 - 73.5）pg x μg（-1）蛋白（p<0.05）。这被抗肿瘤坏死因子-α（TNF-α）、抗白细胞介素-1β（IL-1β）和10（-5）M奈多罗米钠显著减弱。这些发现表明，人支气管上皮细胞衍生的介质可能增强嗜酸性粒细胞活性，且这可被奈多罗米钠调节，提示了其抗炎作用的一种可能机制。
