ScRNA-seq data of BALF and blood cells from COPD and control
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PROVIDER: EGAS00001004369 | EGA |
REPOSITORIES: EGA
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Project description:Alveolar epithelial type II cells (AEC2) strictly regulate lipid metabolism to maintain surfactant synthesis. A loss in AEC2 cell function and surfactant production are implicated in the pathogenesis of the smoking related lung disease, chronic obstructive pulmonary disease (COPD). It is unclear if smoking alters lipid synthesis in AEC2 cells and if altering lipid metabolism in AEC2 cells contributes to COPD development. In this study, high throughput lipidomic analysis revealed increased lipid biosynthesis in AEC2 cells isolated from mice chronically exposed to cigarette smoke (CS). Mice with a targeted deletion of the de novo lipogenesis enzyme, fatty acid synthase (FASN) in AEC2 cells (FasniAEC2) exposed to CS exhibited higher bronchoalveolar lavage fluid (BALF) neutrophils, higher BALF protein, more severe air-space enlargement and were more susceptible to age-induced emphysema. FasniAEC2 mice exposed to CS had lower levels of key surfactant phospholipids but higher levels of BALF ether phospholipids, sphingomyelins and polyunsaturated fatty acid containing-phospholipids, as well as increased BALF surface tension. FasniAEC2 mice exposed to CS also had higher markers of ferroptosis in the lung. These data suggest that AEC2 cell FASN modulates the response of the lung to smoke by regulating the composition of the surfactant phospholipidome.
2023-08-22 | GSE235644 | GEO
Project description:Mucus accumulation is a key feature of respiratory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). This is associated with goblet cell metaplasia and mucin overexpression, which can be induced by the increased activity of neutrophil elastase. The aim of the study was to characterization of mucus and epithelial cell proteomics in a porcine pancreatic elastase (PPE) mouse model of COPD/CF. The major proteins detected in mucus plugs obtained from PPE-treated mice included mucins Muc5ac and Muc5b, mucus-related proteins Clca1, Fcgbp, and Bpifb1. These proteins were upregulated in bronchoalveolar lavage (BAL) fluid and epithelial cells in mice exposed to elastase. Similar changes were found in BAL fluid of COPD patients.
2018-10-22 | PXD006770 | Pride
Project description:Abstract: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease for which there is no cure. Accumulating research results suggest a role for extracellular vesicles (EVs) in the pathogenesis of COPD. This study aimed to uncover the involvement of EVs and their molecular cargo in the progression of COPD by identification of EV-associated protein and microRNA (miRNA) profiles. We isolated EVs from bronchial alveolar lavage fluid (BALF) of 18 patients with COPD and 11 healthy controls by size exclusion chromatography. EV isolates were characterized by Nnanoparticle tracking analysis and protein content. Proteomic analysis revealed higher abundance of 284 proteins (log2FC > 1) and lower abun-dance of 3 proteins (log2FC <-1) in EVs derived from patients with COPD. Ingenuity pathway analysis showed that proteins enriched in COPD-associated EVs trigger inflammatory responses including neutrophil degranulation. Variances in surface receptors and ligands associated with COPD EVs suggested preferential interaction with alveolar cells. Small RNAseq analysis iden-tified higher abundance of ten miRNAs and lower abundance of one in EVs from COPD versus controls (Basemean >100, FDR<0.05). Our data indicate that the molecular composition of EVs in BALF of patients with COPD is altered compared to healthy control EVs. Several components in COPD EVs were identified that may perpetuate inflammation and alveolar tissue destruction.
2024-06-23 | PXD049998 | Pride
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
2022-05-23 | GSE183974 | GEO
Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.
2022-05-23 | GSE183973 | GEO
Project description:Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in chronic obstructive pulmonary disease patients with emphysema. The antimicrobial effects of AZM on the lung microbiome are not known and may contribute to its beneficial effects. Methods. Twenty smokers with emphysema were randomized to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements included: rDNA gene quantity and sequence. Results. Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Conclusions. AZM treatment the lung microbiome Randomized trial comparing azithromycin (AZM) treatment with placebo for eight weeks. Bronchoalveolar lavage (BAL) samples were obtained before and after treatment to explore the effects of AZM on microbiome, in the lower airways. 16S rRNA was quantified and sequenced (MiSeq) The amplicons from total 39 samples are barcoded and the barcode is provided in the metadata_complete.txt file.
2016-07-19 | E-GEOD-74396 | biostudies-arrayexpress
Project description:Background: When exposed to specific stimuli, macrophages exhibit distinct activation programs, M1 and M2 polarization, that define macrophage function as inflammatory/immune effectors or anti-inflammatory/tissue remodeling cells, respectively. Due to their position on the lung epithelial surface, alveolar macrophages (AM) directly interact with environmental stimuli such as cigarette smoke, the major risk factor for the development of chronic obstructive pulmonary disease (COPD). Based on the current paradigm that, in response to smoking, AM contribute to both inflammatory and tissue remodeling processes in the lung relevant to the pathogenesis of COPD, we hypothesized that chronic exposure to cigarette smoking activates both the M1 and M2 polarization programs in AM. Methods and Findings: To assess this hypothesis, global transcriptional profiling with TaqMan confirmation and flow cytometry analysis was carried out on AM obtained by bronchoalveolar lavage of 24 healthy nonsmokers, 34 healthy smokers and 12 smokers with COPD to assess the expression of 41 M1 genes and 32 M2 genes in each group. Contrary to our expectations, while there was up-regulation of some genes typical for M2-related phenotypes, AM of healthy smokers exhibited substantial suppression of M1-related inflammatory/immune genes. These M1- and M2-related changes progressed with the development of smoking-induced lung disease, with AM of smokers with COPD exhibiting further down-regulation of M1-related genes accompanied with further up-regulation of some M2-related genes. Conclusion: The data demonstrates that the modifications of the AM transcriptome associated with smoking result in a unique phenotype characterized by reprogramming of AM towards M1-deactivated partially M2-polarized macrophages and suggests that, while AM likely contribute to smoking-induced tissue remodeling, the role of AM in the early pathogenesis of smoking-induced COPD in humans is not inflammatory. This concept is a departure from the conventional concept that AM-mediated inflammation participates in the early derangements of the lung induced by smoking, and suggests a novel paradigm for conceptualizing COPD and developing new approaches to prevent the development of smoking-induced lung disease. Comparison of gene expression in alveolar macrophages of normal non-smokers and normal smokers and smokers with COPD
2009-08-09 | E-GEOD-13896 | biostudies-arrayexpress
Project description:Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation，obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, e.g. cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking. By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers.
2019-06-21 | GSE133096 | GEO
Project description:DNA methylation patterns in chronic pulmonary obstructive disease (COPD) might offer new insights into disease pathogenesis. To assess methylation profiles in the main COPD target organ, we performed an epigenome-wide association study on bronchoalveolar lavage (BAL) cells. Bronchoscopies were performed in 18 COPD subjects and 15 controls (ex- and current smokers). DNA methylation was measured with Illumina MethylationEPIC BeadChip covering >850,000 CpGs. Differentially methylated positions (DMPs) were examined for 1) enrichment in pathways and functional gene relationships using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology; 2) accelerated aging using Horvath’s epigenetic clock; 3) correlation with gene expression; and 4) colocalization with genetic variation. We found 1,155 Bonferroni significant (P < 6.74 × 10-8) DMPs associated with COPD, many with large effect sizes. Functional analysis identified biologically plausible pathways and gene relationships, including enrichment for transcription factor activity. Strong correlation was found between DNA methylation and chronological age, but not between COPD and accelerated aging. For 79 unique DMPs, DNA methylation correlated significantly with gene expression in BAL cells. Thirty-nine percent of DMPs were co-localized with COPD-associated SNPs. To the best of our knowledge, this is the first EWAS of COPD on BAL cells, and our analyses revealed many differential methylation sites. Integration with mRNA data showed a strong functional readout for relevant genes, identifying sites where DNA methylation might directly impact expression. Almost half of DMPs were co-located with SNPs identified in previous GWAS of COPD, suggesting joint genetic and epigenetic pathways related to disease.
2022-03-17 | GSE198870 | GEO
Project description:Chronic obstructive pulmonary disease (COPD) is diagnosed by airway obstruction and underlies a group of ailments such as bronchitis, emphysema and often asthma; however, rodent models do not resemble human pathology. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, thrombosis, oxidative stress, and suppressed immune function, that are also apparent in COPD patients, we exposed SH and commonly used male Sprague Dawley (SD) to 0, 250, or 350 ppm sulfur dioxide (SO2), 5h/d for 4 consecutive days. Airways disease was characterized by pulmonary functional, pathological and molecular analysis. SO2 caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD. Bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose-dependent and significantly greater in SH than in SD rats. The recovery was incomplete 4-day following SO2 exposure in SH rats. Pulmonary protein leakage did not occur in either strain but lactate dehydrogenase and n-acetyl glucosaminidase activity was increased in BALF of SH rats. Lung pathology and morphometric evaluation of mucin production in the airways demonstrated significantly greater impact of SO2 in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, and impairment cell signaling and fatty acid metabolism in SH rats. Gene expression pattern of SD and SH rats following SO2 exposure demonstrated greater effect on inflammation/immune markers, and oxidative stress. Thus, the SH rat may serve as a better and more susceptible rat strain to be used for experimental model of bronchitis which is relevant to human disease. Experiment Overall Design: Spontaneously hypertensive and Sprague Dawley rats were used in this experiment. Each strain of rat was treated with either SO2 or AIR (control). There were 4 biological replicates for each strain/treatment.
2008-02-23 | E-GEOD-4702 | biostudies-arrayexpress