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

• Published in: American journal of respiratory and critical care medicine 2007-05, Vol.175 (10), p.998-1005
• Main Authors: Demedts, Ingel K, Bracke, Ken R, Van Pottelberge, Geert, Testelmans, Dries, Verleden, Geert M, Vermassen, Frank E, Joos, Guy F, Brusselle, Guy G
• Format: Article
• Language: English
• Subjects: Aged; Airway management; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Chemokine CCL20; Chemokines; Chemokines, CC - analysis; Chemokines, CC - genetics; Chemokines, CC - metabolism; Chronic obstructive pulmonary disease; Chronic obstructive pulmonary disease, asthma; Dendritic cells; Dendritic Cells - immunology; Enzymes; Female; Flow cytometry; Humans; Inflammation; Intensive care medicine; Lung - immunology; Lung - pathology; Lung diseases; Lungs; Macrophage Inflammatory Proteins - analysis; Macrophage Inflammatory Proteins - genetics; Macrophage Inflammatory Proteins - metabolism; Male; Medical sciences; Middle Aged; Neutrophils; Pathogenesis; Pneumology; Proteins; Pulmonary Disease, Chronic Obstructive - immunology; Pulmonary Disease, Chronic Obstructive - pathology; Receptors, CCR6; Receptors, Chemokine - analysis; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; RNA, Messenger - analysis; RNA, Messenger - metabolism; Sputum - chemistry; Sputum - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200608-1113OC

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process. To evaluate the presence of DC in small airways of patients with COPD. We evaluated DC infiltration in small airways by immunohistochemistry in patients with COPD (stage I-IV), never-smokers, and smokers without COPD. Chemokine ligand 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. Chemokine receptor 6 (CCR6, the receptor for CCL20) expression on human pulmonary DC was evaluated by RT-PCR and flow cytometry. 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 adventitia increases along with disease severity. CCL20 mRNA expression in total lung and CCL20 protein levels in induced sputum are significantly 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. 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.