Effect of cigarette smoke on the permeability and IL-1 beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease

Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease (COPD), only a small proportion of s mokers develop the disease. We tested the hypothesis that the response of t he bronchial epithelium to cigarette smoke (CS) differs in patients with CO PD. Such a difference might explain in part why only some cigarette smokers develop the disease. We established primary explant cultures of human bron chial epithelial cells (HBEC) from biopsy material obtained from never-smok ers who had normal pulmonary function, smokers with normal pulmonary functi on, and smokers with COPD, and exposed these for 20 min to CS or air. Measu rements were subsequently made over a period of 24 h of transepithelial per meability and release of interleukin (IL)-1 beta and soluble intercellular adhesion molecule-1 (sICAM-1). In addition, intracellular reduced glutathio ne (GSH) levels were measured after 24 h incubation. Exposure to CS increas ed the permeability of these cultures in all study groups, but the most mar ked 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 (mea n, 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% incre ase 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 cont rast, CS exposure did not influence significantly the release of either med iator from the cells of smokers with normal pulmonary function. Levels of i ntracellular GSH were significantly higher in cultures of HBEC derived from smokers, both those with normal pulmonary function and those with COPD, co mpared with cultures from healthy never-smokers. Exposure to CS significant ly decreased the concentration of intracellular GSH in all cultures. Howeve r, the fall in intracellular GSH was significantly greater in cells from pa tients with COPD (mean 72.9% decrease) than in cells from never-smokers (me an 61.4% decrease; P = 0.048) or smokers with normal pulmonary function (me an 43.9% decrease; P = 0.02). These results suggest that whereas smokers wi th or without COPD demonstrate increased levels of GSH within bronchial epi thelial cell cultures, those with COPD have a greater susceptibility to the effects of CS in reducing GSH levels and causing increased permeability an d release of proinflammatory mediators such as IL-1 beta and sICAM-1.