Mast cells reside at interfaces with the environment, including the mucosa of the respiratory and gastrointestinal tracts. This localization exposes mast cells to inhaled, or ingested, environmental challenges. In the airways of smokers, resident immune cells will be in contact with the condensed components of cigarette
smoke. Mast cells are of particular interest due to their ability to promote
airway remodeling and mucus hypersecretion. Clinical data show increased levels of mast cell-secreted
tryptase and increased numbers of degranulated mast cells in the lavage and bronchial tissue of smokers. Since mast cell-secreted
proteinases (MCPTs), including
tryptases, contribute to pathological
airway remodeling, we investigated the relationship between mast cell
proteinases and
smoke exposure. We exposed a mast cell line to cigarette
smoke condensate (CSC). We show that CSC exposure increases
MCPT levels in mast cells using an assay for
tryptase-type
MCPT activity. We hypothesized that this increase in
MCPT activity reflects a CSC-induced increase in the cytosolic pool of
proteinase molecules, via stimulation of
MCPT transcription. Transcript array data suggested that
mRNA changes in response to CSC were limited in number and peaked after 3 h of CSC exposure. However, we noted marked transcriptional regulation of several
MCPT genes. CSC-induced changes in the
mRNA levels for MCPTs were confirmed using quantitative RT-PCR. Taken together, our data suggest that chronic exposure to cigarette
smoke up-regulates
MCPT levels in mast cells at both the
protein and the
mRNA level. We suggest that the pathological
airway remodeling that has been described in clinical studies of
smoke inhalation may be attributable to
MCPT overproduction in vivo.