Cigarette smoke affects dendritic cell maturation in the small airways of patients with chronic obstructive pulmonary disease

Abstract

The aim of the present study was to characterize and quantify the numbers and expression levels of cells markers associated with dendritic cell (DC) maturation in small airways in current smokers and non-smokers with or without chronic obstructive pulmonary disease (COPD). Lung tissues from the following 32 patients were obtained during resection for lung cancer: Eight smokers with COPD, eight non-smokers with COPD, eight current smokers without COPD and eight non-smokers without COPD, serving as a control. The tissue sections were immunostained for cluster of differentiation (CD)83 ⁺ and CD1a ⁺ to delineate mature and immature DCs, and chemokine receptor type 7 (CCR7 ⁺) to detect DC migratory ability. Myeloid DCs were collected from the lung tissues, and subsequently the CD83 ⁺ and CCR7 ⁺ expression levels in the lung myeloid DCs were detected using flow cytometry. The expression levels of CD83 ⁺, CD1a ⁺ and CCR7 ⁺ mRNA in total lung RNA were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Evident chronic bronchitis and emphysema pathological changes were observed in the lung tissues of patients with COPD. The results revealed that the numbers of CD83 ⁺ and CCR7 ⁺ DCs were reduced but the numbers of CD1a ⁺ DCs were significantly increased in the COPD group as compared with the control group (P<0.05, respectively). Using RT-qPCR, the expression levels of CCR7 ⁺ and CD83 ⁺ mRNA were found to be reduced in the smokers with COPD as compared with the non-smokers without COPD group (P<0.05, respectively). Excessive local adaptive immune responses are key elements in the pathogenesis of COPD. Cigarette smoke may stimulate immune responses by impairing the homing of airway DCs to the lymph nodes and reduce the migratory potential of DCs. The present study revealed that COPD is associated with reduced numbers of mature CD83 ⁺ DCs and lower CCR7 ⁺ expression levels in small airways.