Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes

BMC Research Notes

Jesus F Bermejo-Martin⁸  Victoria Fernandez⁶  Maria C Gallegos⁶  Raúl Ortiz de Lejarazu⁸  Carlos Disdier⁷  Julia Barbado⁴  Sara Rosich⁵  C Alicia San-Jose⁸  Vicente Roig⁷  Agueda Herrero⁷  Lucia Rico⁸  Felipe Bobillo³  David Andaluz-Ojeda³  Milagros del Olmo⁷  Ignacio Martín-Loeches²  Monica Sanchez-Garcia⁷  Lorenzo Socias¹  Raquel Almansa⁸ 

[1] Critical Care Department, Hospital Son Llatzer- SEMICYUC, Ctra. Manacor, km 4, 07198, Palma de Mallorca, Spain;Critical Care Department Parc Tauli, Hospital Universitari de Sabadell Spain and CIBERES/ SEMICYUC, Sabadell, Spain;Critical Care Department, Hospital Clínico Universitario-SACYL/SEMICYUC, Avda Ramón y Cajal 3, E-47005, Valladolid, Spain;Internal Medicine Service, Hospital Clínico Universitario de Valladolid - SACYL, Avda Ramón y Cajal 3, 47005, Valladolid, Spain;Critical Care Department, Hospital Universitari Joan XXIII, Mallafre Guasch 4, Tarragona, 43007, Spain;Microbiology Service, Hospital Son Llatzer, Ctra. Manacor, km 4, 07198, Palma de Mallorca, Spain;Respiratory Medicine Service, Hospital Clínico Universitario-SACYL / SEPAR /CIBERES, Avda Ramón y Cajal 3, 47005, Valladolid, Spain;Infection & Immunity Medical Investigation Unit (IMI), Microbiology and Immunology Service, Hospital Clínico Universitario - IECSCYL, Avda Ramón y Cajal 3, 47005, Valladolid, Spain

关键词: Proteases;    Neutrophil;    Microarray;    Gene;    Expression;    Critical;    COPD;   

Others  :  1166020
DOI  :  10.1186/1756-0500-5-401

 received in 2012-04-19, accepted in 2012-07-24,  发布年份 2012

【 摘 要 】

Background

Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment.

Findings

By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection.

Conclusion

Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.

【 授权许可】

   
2012 Almansa et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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