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. 2011 Mar 31;6(3):e18426.
doi: 10.1371/journal.pone.0018426.

Innate immune responses are increased in chronic obstructive pulmonary disease

Katherine Joanne Baines  1 , Jodie Louise Simpson, Peter Gerard Gibson
Affiliations

Innate immune responses are increased in chronic obstructive pulmonary disease

Katherine Joanne Baines et al. PLoS One. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, however the role of the innate immune response in the pathogenesis of COPD remains unclear.

Methods: Induced sputum was obtained from adults with COPD (n=22), and healthy controls (n=29) and was processed for differential cell counts. The sputum supernatant was assayed for innate immune mediators using ELISA, whilst sputum gene expression was measured using real-time PCR. Peripheral blood neutrophils were isolated and their response to lipopolysaccaride (LPS) stimulation was assessed in a subgroup of participants with COPD (n=13) and healthy controls (n=21).

Results: Participants with COPD had significantly higher protein levels of interleukin (IL)-8, and neutrophil elastase (NE) and detection of oncostatin M (OSM) compared to healthy controls. Gene expression for toll-like receptor (TLR) 2, IL-8 and OSM were also significantly higher in COPD participants. The level of IL-1β, surfactant protein (SP)-A, matrix metalloproteinase (MMP)-9 and TLR4 mRNA was not significantly different between groups. The level of innate immune response markers were highly associated with the presence of sputum neutrophils, each other and the degree of airflow limitation (FEV1/FVC). Peripheral blood neutrophils from participants with COPD had an increased response to stimulation by LPS; with a greater fold increase in the production of IL-8 and MMP-9 protein, and gene expression of IL-8, TLR2 and TLR4.

Conclusions: The innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Gene expression of IL-8 (A), TLR2 (B) and OSM (C) was increased in the airways of participants with COPD (dark grey) compared to healthy controls (light grey).
Data reported as median with the error bar as the 3rd quartile. *p<0.05 versus healthy controls.
Figure 2
Figure 2. IL-8 (A), HNE (B) and MMP-9 (C) protein levels were higher in the airways of participants with COPD (dark grey) compared to healthy controls (light grey).
Data reported as median with the error bar as the 3rd quartile. *p<0.05 versus healthy controls.
Figure 3
Figure 3. Sputum neutrophil % and TLR2 gene expression are significantly correlated (Spearman R = 0.59; p = 0.001).
Figure 4
Figure 4. Peripheral blood neutrophils isolated from participants with COPD (dark grey) had a greater increase in the production of IL-8 (A) and MMP-9 (B) protein and the gene expression of IL-8 (C), TLR2 (D), and TLR4 (E) in response to LPS stimulation compared to healthy controls (light grey).
Data expressed as fold increase versus media control.*p<0.05 versus healthy controls.
See this image and copyright information in PMC

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