Abstract
BackroundCigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM) and alveolar epithelial cells leading to production of inflammatory mediators. This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair. The interaction between pathogen-associated molecular patterns and the host is mediated by pattern recognition receptors (PRR's). In the present study we characterized the expression of Toll-like receptor (TLR)- 2, TLR4 and CD14 on human AM compared to autologous monocytes obtained from patients with COPD, healthy smokers and non-smokers.MethodsThe study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age. The expression of TLR2, TLR4 and CD14 surface molecules on human AM compared to autologous monocytes was assessed ex vivo using FACS analysis. In situ hybridization was performed on bronchoalveolar lavage (BAL) cells by application of the new developed HOPE-fixative.ResultsThe expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and non-smokers was reduced as compared to autologous monocytes. Comparing AM we detected a reduced expression of TLR2 in COPD patients and smokers. In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients.ConclusionOur data suggest a smoke related change in the phenotype of AM's and the cellular response to microbial stimulation which may be associated with impairment of host defenses in the lower respiratory tract.
Highlights
The expression of TLR2, TLR4 and CD14 on alveolar macrophages (AM) from chronic obstructive pulmonary disease (COPD) patients, smokers and nonsmokers was reduced as compared to autologous monocytes
The expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and nonsmokers was reduced as compared to autologous monocytes
In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients
Summary
The study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age. Study design The study population consisted of three groups: 14 COPD patients (11 male, 3 female, FEV1 % predicted: mean 58, range 35–78), 10 healthy smokers (5 male, 5 female, FEV1 % predicted: mean 103, range 92–120), 10 young (6 male, 4 female, FEV1 % predicted: mean 108, range 98– 118) and 7 elderly healthy non-smokers (6 male 1 female, FEV1 % predicted: mean 120, range 113–142). Bronchoscopy and isolation of BAL cells After sedation with midazolam (3–10 mg) and local anesthesia with 2% lidocain bronchoscopically guided lavage was performed according to standard conditions in the middle lobe with instillation of 300 ml 0,9% NaCl. 20 ml aliquots were instilled and immediately reaspirated, recovery was 70–90 % for smokers and non-smokers and 35–68% for COPD patients. Viability was determined by trypan blue dye exclusion and the sample was diluted to a concentration of 106 viable cells/ml
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