Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. It is unclear if dendritic cells (DC) participate in this inflammatory process.


OBJECTIVE
To evaluate the presence of DC in small airways of patients with COPD.


METHODS
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.


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 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.


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.
Demedts
Ingel K
IK
Department of Respiratory Diseases, Ghent University Hospital, B-9000 Ghent, Belgium. M.DemedtsIngelK@UGent.be
Bracke
Ken R
KR
Van Pottelberge
Geert
G
Testelmans
Dries
D
Verleden
Geert M
GM
Vermassen
Frank E
FE
Joos
Guy F
GF
Brusselle
Guy G
GG
D000368:Aged; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology* / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013183:Sputum / Q000737:chemistry / Q000276:immunology
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine