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

Almansa R, Socias L, Sanchez-Garcia M, Martín-Loeches I, del Olmo M, Andaluz-Ojeda D, Bobillo F, Rico L, Herrero A, Roig V, San-Jose CA, Rosich S, Barbado J, Disdier C, de Lejarazu RO, Gallegos MC, Fernandez V, Bermejo-Martin JF - BMC Res Notes (2012)

Bottom Line: 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.Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Investigación Biomédica del Clínico (ibC), Hospital Clínico Universitario de Valladolid, Avda Ramón y Cajal 3, 47005 Valladolid, Spain.

ABSTRACT

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.

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(a) Left: model depicting the physiological roles of neutrophil and complement system. Those genes with relative higher expression in the ICU compared to the no ICU group are depicted in red (modified from KEGG) (b) One-way hierarchical clustering of neutrophil protease genes. Signal intensity data are color-coded such that the intensity of red indicates a relatively high level of expression, while the intensity of blue represents a relatively low level of expression.
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Figure 1: (a) Left: model depicting the physiological roles of neutrophil and complement system. Those genes with relative higher expression in the ICU compared to the no ICU group are depicted in red (modified from KEGG) (b) One-way hierarchical clustering of neutrophil protease genes. Signal intensity data are color-coded such that the intensity of red indicates a relatively high level of expression, while the intensity of blue represents a relatively low level of expression.

Mentions: IPA analysis of the most representative biological functions revealed that those genes showing higher levels of their corresponding transcripts in the ICU group participate principally in four biological functions: [immune response] (Table 2), [severe acute respiratory syndrome], [respiratory infection] (Table 3) and [inflammatory response] (Table 4). Patients in the ICU group not only showed increased neutrophil counts in blood, but also higher levels of RNAm corresponding to a group of proteins known to participate in neutrophil-mediated antimicrobial defense and tissue injury (Figure 1).


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

Almansa R, Socias L, Sanchez-Garcia M, Martín-Loeches I, del Olmo M, Andaluz-Ojeda D, Bobillo F, Rico L, Herrero A, Roig V, San-Jose CA, Rosich S, Barbado J, Disdier C, de Lejarazu RO, Gallegos MC, Fernandez V, Bermejo-Martin JF - BMC Res Notes (2012)

(a) Left: model depicting the physiological roles of neutrophil and complement system. Those genes with relative higher expression in the ICU compared to the no ICU group are depicted in red (modified from KEGG) (b) One-way hierarchical clustering of neutrophil protease genes. Signal intensity data are color-coded such that the intensity of red indicates a relatively high level of expression, while the intensity of blue represents a relatively low level of expression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475085&req=5

Figure 1: (a) Left: model depicting the physiological roles of neutrophil and complement system. Those genes with relative higher expression in the ICU compared to the no ICU group are depicted in red (modified from KEGG) (b) One-way hierarchical clustering of neutrophil protease genes. Signal intensity data are color-coded such that the intensity of red indicates a relatively high level of expression, while the intensity of blue represents a relatively low level of expression.
Mentions: IPA analysis of the most representative biological functions revealed that those genes showing higher levels of their corresponding transcripts in the ICU group participate principally in four biological functions: [immune response] (Table 2), [severe acute respiratory syndrome], [respiratory infection] (Table 3) and [inflammatory response] (Table 4). Patients in the ICU group not only showed increased neutrophil counts in blood, but also higher levels of RNAm corresponding to a group of proteins known to participate in neutrophil-mediated antimicrobial defense and tissue injury (Figure 1).

Bottom Line: 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.Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Investigación Biomédica del Clínico (ibC), Hospital Clínico Universitario de Valladolid, Avda Ramón y Cajal 3, 47005 Valladolid, Spain.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus