A relation between TGF-ß and mast cells tryptase in experimental emphysema models

Chronic obstructive pulmonary disease (COPD) is a multicomponent disease characterized by emphysema and/or chronic bronchitis. The aim of this study was to investigate the effect of cigarette smoke exposure on mast cells and mast cell function in vitro and in vivo in order to get further insight in the role of mast cells in the pathogenesis of emphysema. We investigated whether cigarette smoke changed mast cell properties in murine airways. Besides we studied the effects of cigarette smoke medium (CSM) on bone marrow derived mast cells on tryptase expression CSM induced the expression of mast cell tryptase (MMCP-6) in mast cells. This tryptase expression was found to be caused by the CSM-stimulated production of TGF-b by mast cells and neutralization of TGF-b suppressed the expression of tryptase. This increase in mast cell tryptase expression was also found in an experimental model for emphysema. Exposure of mice to CS induced an increased expression of mast cell tryptase and enhanced the number of mast cells in the airways. In accordance, TGF-b in bronchoalveolar lavage fluid of smoke-exposed animals was also significantly increased. Our study indicates that mast cells may be a source of TGF-b production after CS exposure and that in turn TGF- may change the protease expression in mast cells, which might be important in the pathogenesis of lung emphysema.