Transcriptional changes in alveolar macrophages from adults with asthma after allergen challenge.
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ABSTRACT:
SUBMITTER: Yang J
PROVIDER: S-EPMC8359176 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Transcriptional changes in alveolar macrophages from adults with asthma after allergen challenge.
Yang Jack J Scicluna Brendon P BP van Engelen Tjitske S R TSR Bonta Peter I PI Majoor Christof J CJ Van't Veer Cornelis C de Vos Alex F AF Bel Elisabeth H EH van der Poll Tom T
Allergy 20210112 7
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Project description:Transcriptional changes in alveolar macrophages from adults with asthma after intrabronchial allergen challenge.
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Project description:Mild asthmatics who met the criteria of the IRB approved protocol of Sub-segmental Bronchial Provocation with Allergen were recruited. The subjects were challenged with sensitive allergen through bronchoscopy. Bronchoalveolar lavage (BAL) fluids were collected before and at 48 hours after allergen challegen. From the BAL fluids, alveolar macrophages were purifed and their RNA was extracted. Total 138 genes including five house keeping genes were evaluated. Two samples of alveolar macrophages from single subject, before and 48 hours after allergen challenge, were directly compared in terms of the expression of inflammatory, chemokine, cytokine genes and their receptor genes.
2014-02-01 | E-GEOD-54585 | biostudies-arrayexpress
Project description:Mild asthmatics who met the criteria of the IRB approved protocol of Sub-segmental Bronchial Provocation with Allergen were recruited. The subjects were challenged with sensitive allergen through bronchoscopy. Bronchoalveolar lavage (BAL) fluids were collected before and at 48 hours after allergen challegen. From the BAL fluids, alveolar macrophages were purifed and their RNA was extracted. Total 138 genes including five house keeping genes were evaluated.
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Project description:Asthma is a complex syndrome associated with episodic decompensations provoked by aeroaller-gen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bron-choalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial aller-gen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by pathway analysis and cor-relation with airway inflammation. SBP-Ag induced statistically significant changes in 549 fea-tures that mapped to 72 uniquely identified metabolites. From these features, two distinct induci-ble metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that in-formed the presence of asthma-relevant pathways, including unsaturated fatty acid produc-tion/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen chal-lenge induces distinct metabolic responses in humans, providing insight into pathogenic and pro-tective endotypes in allergic asthma.
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Project description:This protocol outlines a single-site mechanistic study aiming to investigate long RNAs differentially expressed in the airway epithelium of asthma patients both at baseline and in response to segmental airway allergen challenges. Over approximately 14 days, the study spanned three visits: Visit 1: Comprehensive characterization of participants, encompassing lung function testing, methacholine challenge testing, and allergen skin prick testing. Visit 2: Participants underwent bronchoscopy wherein three procedures were performed a. Epithelial brushings were performed in a segmental airway (baseline sample) b. Diluent (inactive control) was instilled into another segmental airway c. A small dose of allergen was administered into a third segmental airway using standardized cat or dust mite allergen extracts. Visit 3 (24 hours or 7 days post Visit 2): Another bronchoscopy was carried out to collect epithelial brushings in the diluent challenged and allergen challenged segments The collected epithelial brush samples underwent analysis for mRNA expression in the epithelial brushings. The study successfully incorporated a total of 23 subjects, which included 18 asthmatics (with stable or well-controlled conditions), 2 allergic non-asthmatics, and 3 non-allergic non-asthmatics.
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