These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.

SummaryThe airway epithelium plays an active role in acute lung inflammation by producing chemotactic factors and by expressing cell adhesion molecules involved in the migration of leucocytes to extravascular spaces. We have reported previously that neutrophil migration to airways can be downmodulated by exogenously administered vitamin E (a-tocopherol). The mechanism for this effect is not well understood, however. The action of a-tocopherol was investigated in human alveolar type II and bronchial epithelial cells stimulated with tumour necrosis factor-a. Treatment of alveolar epithelial cells with a-tocopherol resulted in down-regulated cell surface expression of intercellular adhesion molecule-1 (ICAM-1). On bronchial epithelial cells, both ICAM-1 and vascular adhesion molecule-1 were decreased, leading to diminished adherence of leucocytes to the cells. The production of the neutrophil chemoattractant interleukin-8 was attenuated in both alveolar and bronchial cells. These effects were preceded by reduced activation of the mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK1/2) and p38, as well as down-regulation of nuclear factor-kB. Comparing the effects of a-tocopherol with that of specific inhibitors of MAPK and protein kinase C (PKC) revealed that effects appear to be partly independent of PKC inhibition. These results implicate the anti-inflammatory action of a-tocopherol in addition to its anti-oxidant properties.

BackgroundExposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.MethodsThirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.ResultsThe standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.ConclusionsA cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.

Background: Exposure to seasonal or indoor allergens may cause sensitisation and development of allergic airway diseases. We have previously demonstrated that the non-proteolytic major house dust mite (HDM) allergen Der p 2 stimulates pro-inflammatory responses in bronchial epithelial cells. We aimed to determine if other clinically relevant non-proteolytic aeroallergens originating from HDMs, storage mites, cat, dog, birch and timothy also activate respiratory epithelial cells. Methods: Cultures of human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial cells and alveolar epithelial cell line A549 were exposed to recombinant (r)Der p 2, natural (n)Der f 2, rEur m 2, rLep d 2, rFel d 1, nFel d 1, rCan f 2, rBet v 1 or rPhl p 5a. A panel of secreted mediators and expression of cell adhesion receptors involved in recruitment, survival and adhesion of inflammatory cells in asthmatic airways was assessed. Results: The mite allergens rDer p 2, nDer f 2, rEur m 2 and rLep d 2 as well as the cat and dog allergens rFel d 1, nFel d 1 and rCan f 2 induced granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3α secretion from bronchial epithelial cells as well as surface expression of intracellular adhesion molecule-1. The pollen allergens rBet v 1 and rPhl p 5a from birch and timothy did not activate the cells. None of the studied allergens affected the alveolar epithelial cells. Conclusion: These results show that both mite and structurally unrelated cat and dog allergens can activate respiratory epithelial cells by adjuvant-like protease-independent mechanisms.