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E-GEOD-16972 - COPD-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function
Released on 18 April 2011, last updated on 19 May 2015
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease. Objectives: Among inflammatory cell types, alveolar macrophages appear to have a key role in initiating and/or sustaining disease progression. These cells are derived from peripheral monocytes. Identification of disease and cell type specific gene expression profiles can be revealing and also practically useful in order to diagnose and characterize disease progression and the effect of drug treatment. Methods: We used Affymetrix microarrays to obtain gene expression data of alveolar macrophages and circulating monocytes of COPD and healthy control patients. The microarray results were confirmed by quantitative real-time polymerase chain reaction in multiple patient collections. Measurements and Main Results: We have identified gene sets specifically associated with COPD in alveolar macrophages and also in monocytes. Immune function, responses to stimuli, and cell death related genes appear to be impacted in both cell types. Remarkably, there is an overlapping gene set between the two cell types. Conclusions: Taken together, our data show that COPD-specific gene signatures can be identified and validated, and that the disease also affects peripheral monocytes. Moreover, monocytes and alveolar macrophages carry overlapping gene expression signatures. Our findings further support the notion that altered responsiveness to stimuli is the key characteristic of alveolar macrophages and also of their precursors, peripheral monocytes. Brochoalveolar lavage fluid samples were collected from of COPD and healthy control patients. Alveolar macrophages were isolated using Percoll gradient centrifugation, isolated using CD14+ magnetic beads, and total RNA was extracted using Qiagen RNeasy Kit. The monocyte samples represent a pool of RNA from 5 patients. Total RNA was labeled with biotin and individual samples were hybridized to Affymetrix HG U133A GeneChips. Affymetrix data files were analyzed using GeneSpring 7.3 software. Using a non-parametric statistical test, we compared the gene expression patterns of the COPD and the healthy control patients and identified a set a genes that showed differential expression between the two groups.
transcription profiling by array
Szilard Poliska <email@example.com>, Attila Szanto, Balazs Dezso, Beata Scholtz, Bertalan Mesko, Eszter Csanky, Iain Kilty, Istvan Szatmari, Janos Podani, Lajos Szeles, Laszlo Nagy, Laszlo Takacs
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function. Poliska S, Csanky E, Szanto A, Szatmari I, Mesko B, Szeles L, Dezso B, Scholtz B, Podani J, Kilty I, Takacs L, Nagy L.