Cigarette smoke extract suppresses the maturation and function of bone marrow derived dendritic cells

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered as a major risk factor in the pathogenesis of COPD. The potential role of DCs in the the respiratory tract of smoker's and COPD patients is poorly understood. In aim of this study is to investigate the effects of cigarette smoke extract (CSE) on the maturation, development and function of mouse bone marrow. Bone marrow derived DCs were developed by culturing isolated cells by femurs of BALB/c mice in presence of GM-CSF (20 ng/ml) for 10 days. CSE was added to cells cultures for 10 days. The surface expression of maturation and co-stimulatory markers were CD11C-MHC11-CD83 and CD86, CD40 and CD80, respectively, as measured by FACS analysis. The functional capacity of DCs was measured by uptake of Dextran-FITC as maesured by FACS analysis. The production of TNF-a, IL-6 and IL-12 was measured by ELISA. After 10 days of incubation with CSE, the DCs maturation was significantly decreased (MHCII/CD11C compared to control, P≤0.05) and costimulatory receptors (CD11C/CD 86, CD11C/CD40 compared to control, P≤ 0.05). The cytokine production did not differ between the experimental groups. However, restimulation with CSE resulted is significant less cytokine production of DCs that had been exposed to CSE for 10 days compared to the non exposed cells. In addition, the uptake of FITC-Dextran was significantly decreased in DCs that had been exposed for 10 days to CSE. It cannot be excluded that the exacerbations in COPD patients might be due to a decreased maturation, development and function of DCs induced by cigarette smoke.