Abstract
BackgroundChronic 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.MethodsInduced 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).ResultsParticipants 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.ConclusionsThe innate immune response is increased in the airways and circulating neutrophils in COPD, and may be an important mechanism involved in disease pathogenesis.
Highlights
Chronic obstructive pulmonary disease (COPD) is responsible for a major and increasing burden of illness and death around the world
Since COPD has been proposed as an ‘archetypal disease of innate immunity’ [9] this study investigated the innate immune response in both the airways and peripheral blood neutrophils of participants with COPD compared to their healthy counterparts
We have examined a broad range of innate markers, in both the systemic and airway compartments, examined toll-like receptor (TLR) signalling in response to the TLR4 agonist LPS, and related these changes to smoking status and airflow obstruction
Summary
Chronic obstructive pulmonary disease (COPD) is responsible for a major and increasing burden of illness and death around the world. It is currently the fourth leading cause of death in most industrialised countries, and by the year 2020 it is predicted to be the third leading cause of death worldwide [1]. Persistent innate immune activation has been linked to chronic inflammatory airway diseases such as neutrophilic asthma, bronchiectasis [7] and models of chronic airway disease [8] This activation is thought to be caused by the interaction of PRRs with viruses, bacteria, reactive oxygen species and dead and damaged cells and leads to the development and exacerbations of COPD [9,10]. Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow obstruction, neutrophilic airway inflammation and chronic bacterial colonisation, the role of the innate immune response in the pathogenesis of COPD remains unclear
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