Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 298; no. 2; pp. L261 - L269
• Main Authors: Profita, Mirella, Sala, Angelo, Bonanno, Anna, Riccobono, Loredana, Ferraro, Maria, La Grutta, Stefania, Albano, Giusy Daniela, Montalbano, Angela Marina, Gjomarkaj, Mark
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2010
• Subjects: Aged; Airway management; Cell Adhesion - physiology; Chronic obstructive pulmonary disease; Cigarettes; Dinoprostone - metabolism; Female; Humans; Leukocytes; Lungs; Macrophages - cytology; Macrophages - immunology; Male; Middle Aged; Neutrophil Infiltration - immunology; Neutrophils - cytology; Neutrophils - immunology; Prostaglandin-Endoperoxide Synthases - metabolism; Protein Isoforms - metabolism; Pulmonary Disease, Chronic Obstructive - enzymology; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - immunology; Receptors, Prostaglandin E - metabolism; Smoke - adverse effects; Smoking; Smoking - adverse effects; Sputum - chemistry; Sputum - cytology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.90593.2008

1 Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo; ; 2 Department of Pharmacological Sciences, University of Milan, Milan; and ; 3 Environmental Health Unit, Agenzia Regionale per la Protezione dell'Ambiente, Palermo, Italy Submitted 1 December 2008 ; accepted in final form 4 November 2009 Cigarette smoke is the main cause of chronic obstructive pulmonary disease (COPD), where it can contribute to the observed airway inflammation. PGE 2 is produced within human airways, and both pro- and anti-inflammatory activities have been reported. We quantitated PGE 2 concentrations in induced sputum supernatants from different groups of subjects and correlated the obtained values to neutrophil infiltration as well as to the expression of cyclooxygenase-2 (COX-2). Cigarette smoke extract (CSE) was used to evaluate the effect of smoking on COX-2 and PGE 2 receptor expression as well as on PGE 2 release in neutrophils and alveolar macrophages (AM) obtained from normal donors. The effects of PGE 2 and of PGE receptor agonists and antagonists were evaluated on the adhesion of neutrophil to a human bronchial epithelial cell line (16HBE). PGE 2 levels, COX-2 expression, and neutrophil infiltration were significantly higher in normal smokers and COPD smokers ( P < 0.0001) compared with controls and COPD former smokers. Induced sputum supernatant caused neutrophil adhesion to 16HBE that was significantly reduced, in COPD smokers only, by PGE 2 immunoprecipitation. In vitro experiments confirmed that CSE increased PGE 2 release and COX-2 and PGE 2 receptor expression in neutrophils and AM; PGE 2 enhanced the adhesion of neutrophils to 16HBE, and a specific E-prostanoid 4 (EP 4 ) receptor antagonist blunted its effect. These results suggest that CSE promote the induction of COX-2 and contributes to the proinflammatory effects of PGE 2 in the airways of COPD subjects. alveolar macrophages; neutrophils; cigarette smoke extract; cyclooxygenase-2 Address for reprint requests and other correspondence: M. Profita, Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Via U. La Malfa 153, 90146 Palermo, Italy (e-mail: mirella.profita{at}ibim.cnr.it ).