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Smoking-dependent reprogramming of alveolar macrophage polarization: implication for pathogenesis of chronic obstructive pulmonary disease.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2009 Aug 15; Vol. 183 (4), pp. 2867-83. Date of Electronic Publication: 2009 Jul 27. - Publication Year :
- 2009
-
Abstract
- When exposed to a specific microenvironment, macrophages acquire either M1- or M2-polarized phenotypes associated with inflammation and tissue remodeling, respectively. Alveolar macrophages (AM) directly interact with environmental stimuli such as cigarette smoke, the major risk factor for chronic obstructive pulmonary disease (COPD), a disease characterized by lung inflammation and remodeling. Transcriptional profiling of AM obtained by bronchoalveolar lavage of 24 healthy nonsmokers, 34 healthy smokers, and 12 COPD smokers was performed to test the hypothesis whether smoking alters AM polarization, resulting in a disease-relevant activation phenotype. The analysis revealed that AM of healthy smokers exhibited a unique polarization pattern characterized by substantial suppression of M1-related inflammatory/immune genes and induction of genes associated with various M2-polarization programs relevant to tissue remodeling and immunoregulation. Such reciprocal changes progressed with the development of COPD, with M1-related gene expression being most dramatically down-regulated (p < 0.0001 vs healthy nonsmokers, p < 0.002 vs healthy smokers). Results were confirmed with TaqMan real-time PCR and flow cytometry. Among progressively down-regulated M1-related genes were those encoding type I chemokines CXCL9, CXCL10, CXCL11, and CCL5. Progressive activation of M2-related program was characterized by induction of tissue remodeling and immunoregulatory genes such as matrix metalloproteinase (MMP)2, MMP7, and adenosine A3 receptor (ADORA3). Principal component analysis revealed that differential expression of polarization-related genes has substantial contribution to global AM phenotypes associated with smoking and COPD. In summary, the data provide transcriptome-based evidence that AM likely contribute to COPD pathogenesis in a noninflammatory manner due to their smoking-induced reprogramming toward M1-deactivated, partially M2-polarized macrophages.
- Subjects :
- Adult
Bronchoalveolar Lavage Fluid cytology
Bronchoalveolar Lavage Fluid immunology
Female
Gene Expression Regulation immunology
Humans
Inflammation Mediators pharmacology
Lung immunology
Lung metabolism
Lung pathology
Macrophages, Alveolar classification
Macrophages, Alveolar metabolism
Male
Middle Aged
Nicotine administration & dosage
Oligonucleotide Array Sequence Analysis
Pulmonary Disease, Chronic Obstructive etiology
Cell Polarity immunology
Macrophages, Alveolar immunology
Macrophages, Alveolar pathology
Pulmonary Disease, Chronic Obstructive immunology
Pulmonary Disease, Chronic Obstructive pathology
Smoking immunology
Smoking pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 183
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 19635926
- Full Text :
- https://doi.org/10.4049/jimmunol.0900473