Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.

Szilard Poliska, Eszter Csanky, Attila Szanto, Istvan Szatmari, Bertalan Mesko, Lajos Szeles, Balazs Dezso, Beata Scholtz, Janos Podani, Iain Kilty, Laszlo Takacs, Laszlo Nagy

Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.

Journal Article: Respiration (impact factor: 1.94). 03/2011; 81(6):499-510. DOI: 10.1159/000324297

Abstract

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) derived from peripheral monocytes (MO) appear to play a key role in initiating and/or sustaining disease progression.
To identify disease- and cell type-specific gene expression profiles and potential overlaps in those in order to diagnose COPD, characterize its progression and determine the effect of drug treatment.
Global gene expression analysis was used for primary screening in order to obtain expression signatures of AMs and circulating MOs of COPD patients and healthy controls. The results of microarray analyses of AMs (20 controls and 26 COPD patients) and MOs (16 controls and 22 COPD patients) were confirmed and validated by real-time quantitative polymerase chain reaction.
We have identified gene sets specifically associated with COPD in AMs and MOs. There were overlapping genes between the two cell types. Our data also show that COPD-specific gene expression signatures in AMs and MOs correlate with percent of predicted FEV(1).
Disease-specific and overlapping gene expression signatures can be defined in lung-derived macrophages and also in circulating monocytes. Some of the validated expression changes in both cell types correlate with lung function and therefore could serve as biomarkers of disease progression.

Source: PubMed

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Keywords

16 controls
 
20 controls
 
22 COPD patients
 
26 COPD patients
 
cell type-specific gene expression profiles
 
cell types correlate
 
chronic inflammatory disease
 
Chronic obstructive pulmonary disease
 
co-morbid conditions
 
COPD-specific gene expression signatures
 
diagnose COPD
 
expression signatures
 
Global gene expression analysis
 
healthy controls
 
MOs correlate
 
overlapping gene expression signatures
 
progressive airflow limitation
 
significant extrapulmonary
 
two cell types
 
validated expression changes