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Series GSE13896 Query DataSets for GSE13896
Status Public on Aug 10, 2009
Title Smoking-dependent Reprogramming of Alveolar Macrophage Polarization: Implication for Pathogenesis of COPD
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
 
Overall design Comparison of gene expression in alveolar macrophages of normal non-smokers and normal smokers and smokers with COPD
 
Contributor(s) Shaykhiev R, Krause A, Salit J, Strulovici-Barel Y, Harvey B, O’Connor TP, Crystal RG
Citation(s) 19635926
Submission date Dec 10, 2008
Last update date Mar 25, 2019
Contact name Yael Strulovici-Barel
E-mail(s) yas2003@med.cornell.edu
Organization name Weill Cornell Medical College
Department Department of Genetic Medicine
Lab Crystal
Street address 1300 York Avenue
City New York
State/province NY
ZIP/Postal code 10021
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (70)
GSM219241 alveolar macrophages, non-smoker 001
GSM219242 alveolar macrophages, non-smoker 002
GSM219243 alveolar macrophages, non-smoker 003
Relations
BioProject PRJNA110303

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE13896_RAW.tar 1.5 Gb (http)(custom) TAR (of CEL, CHP)
Processed data included within Sample table
Processed data provided as supplementary file
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