Cigarette smoke increases BLT2 receptor functions in bronchial epithelial cells: in vitro and ex vivo evidence

Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with importantinvolvement in the inflammatory responses of chronic obstructivepulmonary disease (COPD). Airway epithelium is emerging as a regulatorof innate immune responses to a variety of insults including cigarettesmoke, the major risk factor for COPD. In this study we have exploredwhether cigarette smoke extracts (CSE) or soluble mediators present indistal lung fluid samples (mini-bronchoalveolar lavages) from smokersalter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-activated receptor-a (PPAR-a) in bronchial epithelial cells. We alsoevaluated the effects of CSE on the expression of intercellular adhesionmolecule 1 (ICAM-1) and on the binding of signal transducer and activatorof transcription 1 (STAT-1) to ICAM-1 promoter as well as theadhesiveness of neutrophils to bronchial epithelial cells. CSE and minibronchoalveolarlavages from smokers increased BLT2 and ICAM-1expression as well as the adhesiveness of neutrophils to bronchial epithelialcells and decreased PPAR-a expression. CSE induced the activation ofSTAT-1 and its binding to ICAM-1 promoter. These findings suggest that,in bronchial epithelial cells, CSE promote a prevalent induction ofpro-inflammatory BLT2 receptors and activate mechanisms leading toincreased neutrophil adhesion, a mechanism that contributes to airwayneutrophilia and to tissue damage.