Differential expression of mast cells in the small airways and alveolar septa of current smokers and patients with small airway disease and COPD

Abstract

BackgroundCOPD patients suffer from dysregulated and suppressed immune functionality, determined by their loss of degranulating capacity. Here we provide crucial information on the presence of degranulated MC in COPD airways and demonstrate their relationship to lung physiology and airway remodelling.MethodsSmall airway (SA) lung resections from non-smoking controls (NC), smokers with normal lung function (NLFS), small airway disease (SAD), mild-moderate COPD current smokers (CS), and ex-smokers (ES) were dual immuno-stained with mast cell tryptase and degranulation marker LAMP-1. Total MC, degranulating MC and non-MC were enumerated in SA epithelium and sub-epithelium, respectively, and in alveolar septa.ResultsIn the SA wall, sub-epithelial areas, COPD-CS and -ES had significantly lower mast cells than NC (p<0.05), though considerably higher in SA epithelium (p<0.01). Degranulating non-mast cells were higher in SAD (p<0.05) than in COPD in SA sub-epithelium. In contrast, there were significant increases in total mast cells (degranulated and non-degranulated) and degranulated non-mast cells in the alveolar septum of COPD patients compared to NC (p<001). The lower numbers of mast cells in the sub-epithelium correlated with lower FEV1/FVC and FEF25-75%, higher smoking rates in COPD patients, and increased SA wall thickness and ECM. The increase in the alveolar in mast cells negatively correlated with FEF 25-75%.ConclusionsThis study is the first to assess the differential pattern of mast cells, degranulating mast and non-mast cell populations in the SA and alveoli of COPD patients. The spatial positioning of the mast cells within the airways showed variable correlations with lung function.