Leukotriene B4 (LTB4) is a neutrophil chemotactic molecule with important
involvement in the inflammatory responses of chronic obstructive
pulmonary disease (COPD). Airway epithelium is emerging as a regulator
of innate immune responses to a variety of insults including cigarette
smoke, the major risk factor for COPD. In this study we have explored
whether cigarette smoke extracts (CSE) or soluble mediators present in
distal lung fluid samples (mini-bronchoalveolar lavages) from smokers
alter the expression of the LTB4 receptor 2 (BLT2) and peroxisome proliferator-
activated receptor-a (PPAR-a) in bronchial epithelial cells. We also
evaluated the effects of CSE on the expression of intercellular adhesion
molecule 1 (ICAM-1) and on the binding of signal transducer and activator
of transcription 1 (STAT-1) to ICAM-1 promoter as well as the
adhesiveness of neutrophils to bronchial epithelial cells. CSE and minibronchoalveolar
lavages from smokers increased BLT2 and ICAM-1
expression as well as the adhesiveness of neutrophils to bronchial epithelial
cells and decreased PPAR-a expression. CSE induced the activation of
STAT-1 and its binding to ICAM-1 promoter. These findings suggest that,
in bronchial epithelial cells, CSE promote a prevalent induction of
pro-inflammatory BLT2 receptors and activate mechanisms leading to
increased neutrophil adhesion, a mechanism that contributes to airway
neutrophilia and to tissue damage
