A Distinctive Alveolar Macrophage Activation State Induced by Cigarette Smoking
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE2255 | GEO | 2005/12/31
SECONDARY ACCESSION(S): PRJNA91361
REPOSITORIES: GEO
Similar Datasets
Project description:Macrophages are believed to play a central role in emphysema based largely on data from mouse models. However, the relevance of these models to smoking-related lung disease in humans is uncertain.We sought to comprehensively characterize the effects of smoking on gene expression in human alveolar macrophages and to compare these with effects seen in transgenic mouse models of emphysema.We used DNA microarrays with genomewide coverage to analyze alveolar macrophages from 15 smokers, 15 nonsmokers, and 15 subjects with asthma (disease control). Selected gene expression changes were validated by polymerase chain reaction and ELISA. Expression changes were compared with those identified by microarray analysis of interleukin-13-overexpressing and integrin-beta6-deficient mice, which both develop emphysema.All 15 smokers shared a common pattern of macrophage gene expression that distinguished them from nonsmokers, a finding not observed in subjects with asthma. We identified 110 genes as differentially expressed in smokers despite using conservative statistical methods. Matrix metalloproteinase 12, a proteinase that plays a critical role in mouse models, was the third most highly induced gene in smokers (ninefold, p < 0.0001). However, most changes in smokers were not reflected in mouse models. One such finding was increased osteopontin expression in smokers (fourfold, p = 0.006), which was confirmed at the protein level and correlated with the degree of airway obstruction.Smoking induces a remarkably consistent and distinctive pattern of alveolar macrophage activation. These studies identify aspects of mouse models that are directly relevant to human smokers and also reveal novel potential mediators of smoking-related diseases.
| S-EPMC2718436 | biostudies-literature
Project description:Cigarette smoking is the leading cause of emphysema in the United States. Alveolar macrophages play a critical role in the inflammation-mediated remodeling of the lung parenchyma in emphysema. However, the exact gene pathways and the role of DNA methylation in moderating this pathological transformation are not known. In order to more exactly understand this process, we compared genome-wide expression and methylation signatures of alveolar macrophages isolated from heavy smokers with those isolated from non-smoking controls. We found enrichment of differential methylation in genes from immune system and inflammatory pathways as determined by standard pathway analysis. Consistent with recent findings, significant methylation changes were particularly enriched in the areas flanking CpG islands (CpG shores). Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune system and inflammatory pathways. We conclude that alveolar macrophages from the lungs of smokers demonstrate coordinated changes in DNA methylation and gene expression that link to inflammation pathways. We suggest that further studies of DNA methylation in immune and inflammation-related gene expression are needed to understand the pathogenesis of emphysema and other smoking-related diseases. Expression analysis of 13 smokers vs. 10 non-smokers on the Affymetrix Exon Array. This submission represents the expression component of the study.
2011-02-03 | E-GEOD-27002 | biostudies-arrayexpress
Project description:Cigarette smoking is the leading cause of emphysema in the United States. Alveolar macrophages play a critical role in the inflammation-mediated remodeling of the lung parenchyma in emphysema. However, the exact gene pathways and the role of DNA methylation in moderating this pathological transformation are not known. In order to more exactly understand this process, we compared genome-wide expression and methylation signatures of alveolar macrophages isolated from heavy smokers with those isolated from non-smoking controls. We found enrichment of differential methylation in genes from immune system and inflammatory pathways as determined by standard pathway analysis. Consistent with recent findings, significant methylation changes were particularly enriched in the areas flanking CpG islands (CpG shores). Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune system and inflammatory pathways. We conclude that alveolar macrophages from the lungs of smokers demonstrate coordinated changes in DNA methylation and gene expression that link to inflammation pathways. We suggest that further studies of DNA methylation in immune and inflammation-related gene expression are needed to understand the pathogenesis of emphysema and other smoking-related diseases.
2011-02-03 | GSE27002 | GEO
Project description:Alveolar macrophages from never smokers and active smokers were isolated by bronchoalveolar lavage and gene expression was measured. Chronic cigarette smoke exposure, as occurs in smoker's lungs, leads to significant changes in gene expression. Of note, RNA was isolated immediately following bronchoscopy. Alveolar macrophage levels were >95%. 4 never smokers and 4 active smokers were recruited for the study. After bronchoalveolar lavage and RNA isolation, gene expression was measured using Affymetrix Human Exon 1.0 ST arrays.
2012-10-02 | E-GEOD-34517 | biostudies-arrayexpress
Project description:Alveolar macrophages from never smokers and active smokers were isolated by bronchoalveolar lavage and gene expression was measured. Chronic cigarette smoke exposure, as occurs in smoker's lungs, leads to significant changes in gene expression. Of note, RNA was isolated immediately following bronchoscopy. Alveolar macrophage levels were >95%.
2012-10-02 | GSE34517 | GEO
Project description:In our lower respiratory tract, the alveolar spaces are divided from the bloodstream and the external environment by only a few microns of interstitial tissue. Alveolar macrophages (AMs) defend this delicate mucosal surface from invading infections by regularly patrolling the site. AMs have three behaviour modalities to achieve this goal: extending cell protrusions to sample surrounding areas, squeezing the whole cell body between alveoli, and patrolling by moving the cell body around each alveolus. In this study we found Rho GTPase, cell division control protein 42 (CDC42) expression significantly decreased after berry-flavoured e-cigarette (e-cig) exposure. This resulted in a shift in AM behaviour from squeezing to probing. Changes in AM behaviour led to a reduction in the clearance of inhaled bacteria, Pseudomonas aeruginosa. These findings shed light on pathways involved in AM migration and highlight the harmful impact of e-cigarette vaping on alveolar macrophage function.
2024-09-04 | PXD050380 | Pride
Project description:This project is based upon the fundamental observation that alveolar macrophage-derived extracellular vesicles (AM-EVs), when internalized by neighboring epithelial cells, inhibit their infection by influenza virus. This inhibitory activity of AM-EVs is abolished when AMs are treated with cigarette smoke extract (CSE). We chose to survey the AM-EV proteome in an effort to identify candidate proteins whose abundance within EVs was downregulated by CSE treatment of AMs, thus explaining the ability of CSE to abrogate the inhibitory activity against influenza.
2020-06-09 | PXD019528 | Pride
Project description:This series represents isolated alveolar macrophages from human subjects.
2008-06-12 | E-GEOD-2125 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD pathogenesis is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures, as well as macrophages, accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to increased lung compliance, total lung capacity, and mean linear chord length in WT, but not B cell-deficient mice, associated with an increased size and number of iBALT structures. The increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro co-culture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation. In summary, B cell function in iBALT formation in CS-induced emphysema provides a new innovative mechanism, which could be explored as a target for therapeutic intervention in COPD patients. Expression data of mice treated with cigarette smoke. Lung tissue was analysed at four and six months of age.
2014-12-04 | E-GEOD-52509 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD pathogenesis is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures, as well as macrophages, accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to increased lung compliance, total lung capacity, and mean linear chord length in WT, but not B cell-deficient mice, associated with an increased size and number of iBALT structures. The increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro co-culture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation. In summary, B cell function in iBALT formation in CS-induced emphysema provides a new innovative mechanism, which could be explored as a target for therapeutic intervention in COPD patients.
2014-12-04 | GSE52509 | GEO