Accumulation of Dendritic Cells and Increased CCL20 Levels in the Airways of Patients with Chronic Obstructive Pulmonary Disease

Abstract

Rationale: Chronic obstructive pulmonary disease (COPD) is charac- terized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process. Objectives: To evaluate the presence of DC in small airways of pa- tients with COPD. Methods: We evaluated DC infiltration in small airways by immuno- histochemistry in patients with COPD (stage I-IV), never-smokers, and smokerswithout COPD. Chemokineligand 20 (CCL20,the most potent chemokine in attracting DC) was determined in total lung by RT-PCR and in induced sputum by enzyme-linked immunsorbent assay.Chemokinereceptor6(CCR6,thereceptorforCCL20)expres- sion on human pulmonary DC was evaluated by RT-PCR and flow cytometry. Measurements and Main Results: There is a significant increase in DC number in the epithelium (p 0.007) and adventitia (p 0.009) of small airways of patients with COPD compared with never-smokers and smokers without COPD. DC number in epithelium and adventi- tia increases along with disease severity. CCL20 mRNA expression in total lung and CCL20 protein levels in induced sputum are signifi- cantly higher in patients with COPD compared with never-smokers (p 0.034 for CCL20 mRNA and p 0.0008 for CCL20 protein) and smokers without COPD (p 0.016 for CCL20 mRNA and p 0.001 for CCL20 protein). DC isolated from human lung express CCR6 both at mRNA and at protein level. Conclusions: This is the first description of airway infiltration by DC in COPD. Moreover, interaction between CCL20 and CCR6 provides a possible mechanism for accumulation of DC in the lungs in COPD.