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Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients
Daniel Droemann1, Torsten Goldmann, Thorsten Tiedje
1Medical Clinic, Research Center Borstel, 23845 Borstel, Germany. ddroemann@fz-borstel.de
Background:
Cigarette 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.
Methods:
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. 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.
Results:
The 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.
Conclusion:
Our 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.
Insights
Cigarette smoke alters immune cells in the lungs, reducing their ability to detect pathogens. This may impair defenses in chronic obstructive pulmonary disease (COPD) patients and smokers.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Cigarette smoke, including lipopolysaccharide (LPS), activates lung cells, contributing to chronic obstructive pulmonary disease (COPD) pathogenesis.
- Respiratory infections trigger exacerbations in COPD, involving pathogen recognition by host receptors.
- Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), mediate host-pathogen interactions.
Purpose of the Study:
- To investigate the expression of Toll-like receptor (TLR) 2, TLR4, and CD14 on alveolar macrophages (AMs) and monocytes.
- To compare these receptor expressions in patients with COPD, healthy smokers, and healthy non-smokers.
Main Methods:
- Studied 14 COPD patients, 10 healthy smokers, and 17 non-smokers.
- Assessed TLR2, TLR4, and CD14 surface molecule expression on AMs and monocytes using flow cytometry (FACS).
- Utilized in situ hybridization with HOPE-fixative on bronchoalveolar lavage (BAL) cells.
Main Results:
- Expression of TLR2, TLR4, and CD14 was lower on AMs from all groups compared to autologous monocytes.
- COPD patients and smokers showed reduced TLR2 expression on AMs.
- LPS stimulation increased TLR2 mRNA and protein in non-smokers' AMs, but not in smokers' or COPD patients' AMs.
Conclusions:
- Smoking appears to alter the phenotype of alveolar macrophages.
- These changes may lead to a diminished cellular response to microbial stimulation.
- Impaired host defenses in the lower respiratory tract could be associated with these smoke-induced alterations.
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