Mast cell mediators in airway remodeling.

Increasing evidence indicates that airway remodeling plays an important part in asthma pathogenesis. However, mechanisms underlying airway remodeling are not yet fully elucidated. Plasminogen activator inhibitor (PAI)-1 is the main inhibitor of the fibrinolytic system and is known to play an essential role in tissue remodeling. Recent evidence indicates that chronic asthma may lead to tissue remodeling such as subepithelial fibrosis and extracellular matrix (ECM) deposition in the airways. Recently, the mast cell (MC), which plays a major role in asthma, is found as a novel source of PAI-1 and a large number of MCs expressing PAI-1 are infiltrated in the airways of patients with severe asthma. Furthermore, PAI-1-deficient mice show reduced ECM deposition in the airways of a murine model of chronic asthma. In a human study, the 4G allele frequency was significantly higher in the asthmatic patients than in the control group. In view of the findings that the 4G allele is associated with elevated plasma PAI-1 level, elevated PAI-1 level in the lung may contribute to the development of airway remodeling. In summary, MCs may play an important role in the pathogenesis of asthma in part by producing PAI-1. Further studies evaluating the mechanisms of PAI-1 action may provide a new paradigm in airway remodeling and lead to the development of a novel therapeutic target.