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

¹ Department of Respiratory Medicine and Allergology, Lund University Hospital, and ² Department of Experimental Medical Science, Lund University, Lund, Sweden

Correspondence and requests for reprints should be addressed to Jonas Erjefält, Ph.D., Airway Inflammation Unit, Dept. of Experimental Medical Science, BMC D12, Lund University, SE-22184, Lund, Sweden. E-mail: jonas.erjefalt{at}med.lu.se

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 (MC_T and MC_TC, respectively) were analyzed in several lung regions.

Measurements and Main Results: In all compartments of COPD lungs, especially at severe stages, the MC_TC population increased in density, whereas the MC_T 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 MC_T and MC_TC 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.

Key Words: mast cells • COPD • chymase • tryptase • apoptosis

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Mast cells are part of the resident immune system in the human lung. They have recently been ascribed roles of potential importance to chronic obstructive pulmonary disease (COPD). Yet, mast cells have only rarely been studied in lungs from COPD patients. What This Study Adds to the Field This study shows that the mast cell populations in the lung are altered in COPD, as exemplified by a change in the connective tissue/mucosal–mast cell balance, altered tissue distribution, and modified morphological and molecular characteristics. Collectively, our data show alterations in lung mast cells in COPD that correlate with lung function and may have significant pathophysiological consequences.

 

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