Alterations in Lung Mast Cell Populations in Patients with Chronic Obstructive Pulmonary Disease

Abstract

Rationale: Mast cells have important roles in innate immunity and tissue remodeling but have remained poorly studied in inflammatory airway diseases like chronic obstructive pulmonary disease (COPD). Objectives: To perform a detailed histological characterization of human lung mast cell populations at different severities of COPD, comparing with smoking and never-smoking control subjects. Methods: Mast cells were analyzed in lung tissues from patients with mild to very severe COPD, GOLD I–IV (n = 25, 10 of whom were treated with corticosteroids). Never-smokers and smokers served as controls. The density, morphology, and molecular characteristics of mucosal and connective tissue mast cells (MCT and MCTC, respectively) were analyzed in several lung regions. Measurements and Main Results: In all compartments of COPD lungs, especially at severe stages, the MCTC population increased in density, whereas the MCT population decreased. The net result was a reduction in total mast cell density. This phenomenon was paralleled by increased numbers of luminal mast cells, whereas the numbers of terminal transferase dUTP nick end labeling (TUNEL)+ apoptotic mast cells remained unchanged. In COPD lungs, the MCT and MCTC populations showed alterations in morphology and expression of CD88 (C5a-R), transforming growth factor (TGF)-β, and renin. Statistically significant correlations were found between several COPD-related mast cell alterations and lung function parameters. Conclusions: As COPD progresses to its severe stages, the mast cell populations in the lung undergo changes in density, distribution, and molecular expression. In COPD lungs, these novel histopathological features were found to be correlated to lung function and they may thus have clinical consequences.