Accumulation of dendritic cells and increased CCL20 levels in the airways of patients with chronic obstructive pulmonary disease.

RATIONALE Chronic obstructive pulmonary disease (COPD) is characterized 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 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. 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 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.

[1]  A. Bergeron,et al.  Characterisation of dendritic cell subsets in lung cancer micro-environments , 2006, European Respiratory Journal.

[2]  G. Joos,et al.  Cigarette Smoke-Induced Pulmonary Inflammation and Emphysema Are Attenuated in CCR6-Deficient Mice1 , 2006, The Journal of Immunology.

[3]  Alan D. Lopez,et al.  Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data , 2006, The Lancet.

[4]  K. Rabe,et al.  Update in chronic obstructive pulmonary disease 2005. , 2006, American journal of respiratory and critical care medicine.

[5]  S. Sethi,et al.  Airway inflammation and bronchial bacterial colonization in chronic obstructive pulmonary disease. , 2006, American journal of respiratory and critical care medicine.

[6]  G. Joos,et al.  Different roles for human lung dendritic cell subsets in pulmonary immune defense mechanisms. , 2006, American journal of respiratory cell and molecular biology.

[7]  R. Pauwels,et al.  Elevated MMP-12 protein levels in induced sputum from patients with COPD , 2005, Thorax.

[8]  J. Hogg Why does airway inflammation persist after the smoking stops? , 2006, Thorax.

[9]  R. Pauwels,et al.  Matrix Metalloproteinase-12 and Cathepsin D Expression in Pulmonary Macrophages and Dendritic Cells of Cigarette Smoke-Exposed Mice , 2005, International Archives of Allergy and Immunology.

[10]  R. Pauwels,et al.  Pulmonary dendritic cells. , 2005, American journal of respiratory and critical care medicine.

[11]  R. Pauwels,et al.  Time course of cigarette smoke-induced pulmonary inflammation in mice , 2005, European Respiratory Journal.

[12]  D. Postma,et al.  Relation between duration of smoking cessation and bronchial inflammation in COPD , 2005, Thorax.

[13]  R. Pauwels,et al.  Matrix metalloproteinases in asthma and COPD. , 2005, Current opinion in pharmacology.

[14]  R. Pauwels,et al.  Identification and characterization of human pulmonary dendritic cells. , 2005, American journal of respiratory cell and molecular biology.

[15]  A. Iwasaki,et al.  Toll-like receptor control of the adaptive immune responses , 2004, Nature Immunology.

[16]  J. Hogg,et al.  Pathophysiology of airflow limitation in chronic obstructive pulmonary disease , 2004, The Lancet.

[17]  R. Pauwels,et al.  Burden and clinical features of chronic obstructive pulmonary disease (COPD) , 2004, The Lancet.

[18]  P. Paré,et al.  The nature of small-airway obstruction in chronic obstructive pulmonary disease. , 2004, The New England journal of medicine.

[19]  W. MacNee,et al.  Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper , 2004, European Respiratory Journal.

[20]  V. Lagente,et al.  Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease , 2004, Inflammation Research.

[21]  H. Hammad,et al.  Taking our breath away: dendritic cells in the pathogenesis of asthma , 2003, Nature Reviews Immunology.

[22]  R. Pauwels,et al.  Chronic obstructive pulmonary disease: molecular and cellularmechanisms , 2003, European Respiratory Journal.

[23]  Lung-Chi Chen,et al.  Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter. , 2003, American journal of respiratory cell and molecular biology.

[24]  P. Hogendoorn,et al.  Aberrant Chemokine Receptor Expression and Chemokine Production by Langerhans Cells Underlies the Pathogenesis of Langerhans Cell Histiocytosis , 2003, The Journal of experimental medicine.

[25]  P. Panina-Bordignon,et al.  Chemokines and their receptors in asthma and chronic obstructive pulmonary disease , 2003, Current opinion in pulmonary medicine.

[26]  L. Nicod,et al.  Superoxide anions induce the maturation of human dendritic cells. , 2003, American journal of respiratory and critical care medicine.

[27]  C. Caux,et al.  REGULATION OF DENDRITIC CELL RECRUITMENT BY CHEMOKINES , 2002, Transplantation.

[28]  Y. Mullen,et al.  Prevention of primary nonfunction of canine islet autografts by treatment with pravastatin. , 2002, Transplantation.

[29]  Ruslan Medzhitov,et al.  Toll-like receptors and innate immunity , 2001, Nature Reviews Immunology.

[30]  David E. Misek,et al.  Profiling Changes in Gene Expression during Differentiation and Maturation of Monocyte-derived Dendritic Cells Using Both Oligonucleotide Microarrays and Proteomics* , 2001, The Journal of Biological Chemistry.

[31]  R. Pauwels,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. , 2001, American journal of respiratory and critical care medicine.

[32]  W. Gong,et al.  Expression of CCR6 and CD83 by cytokine-activated human neutrophils. , 2000, Blood.

[33]  A. Foussat,et al.  Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells. , 2000, Blood.

[34]  C. Caux,et al.  Macrophage Inflammatory Protein 3α Is Expressed at Inflamed Epithelial Surfaces and Is the Most Potent Chemokine Known in Attracting Langerhans Cell Precursors , 2000, The Journal of experimental medicine.

[35]  R. Rabin,et al.  CC-Chemokine Receptor 6 Is Expressed on Diverse Memory Subsets of T Cells and Determines Responsiveness to Macrophage Inflammatory Protein 3α , 1999, The Journal of Immunology.

[36]  M. Goldman,et al.  Oxidative stress up‐regulates IL‐8 and TNF‐α synthesis by human dendritic cells , 1998, European journal of immunology.

[37]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[38]  S. Shapiro,et al.  Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. , 1997, Science.

[39]  T. Mcclanahan,et al.  CCR6, a CC Chemokine Receptor that Interacts with Macrophage Inflammatory Protein 3α and Is Highly Expressed in Human Dendritic Cells , 1997, The Journal of experimental medicine.

[40]  A. Mantovani,et al.  Cloning and Characterization of a Specific Receptor for the Novel CC Chemokine MIP-3α from Lung Dendritic Cells , 1997, The Journal of experimental medicine.

[41]  Naiem A. Zeid,et al.  Tobacco smoke induced lung granulomas and tumors: Association with pulmonary langerhans cells , 1995, Pathology.

[42]  H. Hoogsteden,et al.  Distribution and immunophenotype of mononuclear phagocytes and dendritic cells in the human lung. , 1994, American journal of respiratory cell and molecular biology.

[43]  T. Ley,et al.  Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. , 1993, The Journal of biological chemistry.

[44]  P. Soler,et al.  Cigarette smoking-induced changes in the number and differentiated state of pulmonary dendritic cells/Langerhans cells. , 1989, The American review of respiratory disease.

[45]  V. Ferrans,et al.  Accumulation of Langerhans' cells on the epithelial surface of the lower respiratory tract in normal subjects in association with cigarette smoking. , 1988, The American review of respiratory disease.

[46]  M. Kaliner,et al.  Dendritic cells with antigen-presenting capability reside in airway epithelium, lung parenchyma, and visceral pleura , 1986, The Journal of experimental medicine.

[47]  R. Crystal,et al.  Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema. , 1981, Science.