Airway ß-Defensin-1 Protein Is Elevated in COPD and Severe Asthma.

BACKGROUND: Innate immune antimicrobial peptides, including ß-defensin-1, promote the chemotaxis and activation of several immune cells. The role of ß-defensin-1 in asthma and chronic obstructive pulmonary disease (COPD) remains unclear. METHODS: Induced sputum was collected from healthy controls and individuals with asthma or COPD. ß-defensin-1 protein in sputum supernatant was quantified by ELISA. Biomarker potential was examined using receiver operating characteristic curves. ß-defensin-1 release from primary bronchial epithelial cells (pBECs) was investigated in culture with and without cigarette smoke extract (CSE). RESULTS: Airway ß-defensin-1 protein was elevated in COPD participants compared to asthma participants and healthy controls. Inflammatory phenotype had no effect on ß-defensin-1 levels in asthma or COPD. ß-defensin-1 protein was significantly higher in severe asthma compared to controlled and uncontrolled asthma. ß-defensin-1 protein could predict the presence of COPD from both healthy controls and asthma patients. Exposure of pBECs to CSE decreased ß-defensin-1 production in healthy controls; however in pBECs from COPD participants the level of ß-defensin-1 remanied unchanged. CONCLUSIONS: Elevated ß-defensin-1 protein is a feature of COPD and severe asthma regardless of inflammatory phenotype. ß-defensin-1 production is dysregulated in the epithelium of patients with COPD and may be an effective biomarker and potential therapeutic target.

The placental protein syncytin-1 impairs antiviral responses and exaggerates inflammatory responses to influenza.

BACKGROUND: Pregnancy increases susceptibility to influenza. The placenta releases an immunosuppressive endogenous retroviral protein syncytin-1. We hypothesised that exposure of peripheral monocytes (PBMCs) to syncytin-1 would impair responses to H1N1pdm09 influenza. METHODS AND FINDINGS: Recombinant syncytin-1 was produced. PBMCs from non-pregnant women (n=10) were exposed to H1N1pdm09 in the presence and absence of syncytin-1 and compared to responses of PBMCs from pregnant women (n=12). PBMCs were characterised using flow cytometry, release of interferon (IFN)-α, IFN-λ, IFN-γ, IL-10, IL-2, IL-6 and IL-1ß were measured by cytometric bead array or ELISA. Exposure of PBMCs to H1N1pdm09 resulted in the release of IFN-α, (14,787 pg/mL, 95% CI 7311-22,264 pg/mL) IFN-λ (1486 pg/mL, 95% CI 756-2216 pg/mL) and IFN-γ (852 pg/mL, 95% CI 193-1511 pg/mL) after 48 hours. This was significantly impaired in pregnant women (IFN-α; p<0.0001 and IFN-λ; p<0.001). Furthermore, in the presence of syncytin-1, PBMCs demonstrated marked reductions in IFN-α and IFN-λ, while enhanced release of IL-10 as well as IL-6 and IL-1ß. CONCLUSIONS: Our data indicates that a placental derived protein, syncytin-1 may be responsible for the heightened vulnerability of pregnant women to influenza.

Differential injurious effects of ambient and traffic-derived particulate matter on airway epithelial cells.

BACKGROUND AND OBJECTIVE: Exposure to airborne particulate matter (PM) may promote development of childhood asthma and trigger acute exacerbations of existing asthma via injury to airway epithelial cells (AEC). METHODS: We compared the response of AEC to ambient particulates with median aerodynamic diameters of <10 µm or <2.5 µm from the Sydney metropolitan region (Sydney PM10 or PM2.5), to traffic-derived particulates from the exhaust stack of a motorway tunnel or to inert carbon black as a control. RESULTS: Sydney PM10 strongly stimulated messenger RNA expression and secretion of the pro-inflammatory cytokines interleukin 6 (IL-6) and chemokine (C-X-C motif) ligand 1 (CXCL1) by mouse tracheal AEC. In contrast, traffic-derived particulates did not. Similarly, PM10 stimulated expression of IL6, IL8 and IL1B by human AEC. Mass spectrometric analysis showed that PM10 contained much higher levels of elements associated with dusts of geological origin. In contrast, tunnel soot contained much higher levels of various organic compounds, notably including long straight-chain alkanes and diesel-derived polycyclic aromatic hydrocarbons. Sydney PM2.5, as well as PM10 collected during a period including a major dust storm, both of which contained relatively lower levels of iron but similar levels of other crustal elements, did not stimulate expression or secretion of CXCL1 by mouse AEC. CONCLUSIONS: Ambient PM10 is likely to be more important than traffic-derived PM in causing injury to AEC leading to production of pro-inflammatory cytokines. The injurious effects may be related to the presence of iron in the coarse fraction of airborne PM. These findings are likely to be relevant to the pathogenesis of asthma.