Effect of cigarette smoke on the permeability and IL-1β and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease
Effect of cigarette smoke on the permeability and IL-1β and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease
复制标题
DOI：
10.1165/ajrcmb.23.4.3959
复制
发表时间：
2000-10-01
影响因子：
6.4
通讯作者：
Lozewicz, S
中科院分区：
文献类型：
--
作者：
Rusznak, C;Mills, PR;Lozewicz, S
尽管吸烟在慢性阻塞性肺疾病(COPD)的发展中至关重要，但只有一小部分吸烟者会患上这种疾病。我们验证了一种假设，即COPD患者对香烟烟雾(CS)的反应不同。这种差异可能在一定程度上解释了为什么只有一些吸烟者患上了这种疾病。我们从肺功能正常的非吸烟者、肺功能正常的吸烟者和COPD吸烟者的活检材料中建立了人支气管上皮细胞(HBEC)的原代培养体系，并将其暴露于CS或空气中20min。随后在24小时内进行跨上皮通透性和释放白介素1β和可溶性细胞间黏附分子-1的测定。孵育24 h后，测定细胞内还原型谷胱甘肽(GSH)水平。在所有研究组中，暴露于CS增加了这些培养物的渗透性，但在COPD患者的培养物中观察到最显著的影响(平均增加了85.5%)。CS对肺功能正常的人脐静脉内皮细胞通透性的影响最小(平均为25.0%)，显著低于非吸烟者(平均为53.4%)(P<；0.001)。与暴露于空气中相比，非吸烟组和慢性阻塞性肺病组培养上清液中IL-1β和sICAM-1的释放均显著增加(暴露后24 h IL-1β平均增加250.0%，sICAM-1平均增加175.3%)。相比之下，CS暴露并未显著影响肺功能正常的吸烟者细胞中任一介质的释放。在来自吸烟者的HBEC培养中，无论是肺功能正常的人还是COPD患者，细胞内GSH水平都显著高于健康不吸烟者的培养物。CS可显著降低所有培养细胞内GSH浓度。然而，慢性阻塞性肺疾病患者细胞内GSH的下降(平均下降72.9%)明显大于非吸烟者(平均下降61.4%；P=0.048)和吸烟者(平均下降43.9%；P=0.02)。这些结果表明，尽管患有或不患有COPD的吸烟者在支气管上皮细胞培养中显示出更高的GSH水平，但患有COPD的吸烟者更容易受到CS降低GSH水平的影响，并导致促炎介质如IL-1β和sICAM-1的通透性和释放增加。
Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease (COPD), only a small proportion of smokers develop the disease. We tested the hypothesis that the response of the bronchial epithelium to cigarette smoke (CS) differs in patients with COPD. Such a difference might explain in part why only some cigarette smokers develop the disease. We established primary explant cultures of human bronchial epithelial cells (HBEC) from biopsy material obtained from never-smokers who had normal pulmonary function, smokers with normal pulmonary function, and smokers with COPD, and exposed these for 20 min to CS or air. Measurements were subsequently made over a period of 24 h of transepithelial permeability and release of interleukin (IL)-1 beta and soluble intercellular adhesion molecule-1 (sICAM-1). In addition, intracellular reduced glutathione (GSH) levels were measured after 24 h incubation. Exposure to CS increased the permeability of these cultures in all study groups, but the most marked effect was observed in cultures from patients with COPD (mean increase, 85.5%). The smallest CS-induced increase in the permeability was observed in HBEC cultured from smokers with normal pulmonary function (mean, 25.0%), and this was significantly lower than that of HBEC from never-smokers (mean, 53.4%) (P < 0.001). Compared with exposure to air, exposure to CS led to a significantly increased release of these mediators from cultures of the never-smoker group (mean 250.0% increase in IL-1 beta and mean 175.3% increase in sICAM-1 24 h after exposure) and COPD group (mean 383.3% increase in IL-1 beta and mean 97.4% increase in sICAM-1 24 h after exposure). In contrast, CS exposure did not influence significantly the release of either mediator from the cells of smokers with normal pulmonary function. Levels of intracellular GSH were significantly higher in cultures of HBEC derived from smokers, both those with normal pulmonary function and those with COPD, compared with cultures from healthy never-smokers. Exposure to CS significantly decreased the concentration of intracellular GSH in all cultures. However, the fall in intracellular GSH was significantly greater in cells from patients with COPD (mean 72.9% decrease) than in cells from never-smokers (mean 61.4% decrease; P = 0.048) or smokers with normal pulmonary function (mean 43.9% decrease; P = 0.02). These results suggest that whereas smokers with or without COPD demonstrate increased levels of GSH within bronchial epithelial cell cultures, those with COPD have a greater susceptibility to the effects of CS in reducing GSH levels and causing increased permeability and release of proinflammatory mediators such as IL-1 beta and sICAM-1.