The Inflammatory Effect of Iron Oxide and Silica Particles on Lung Epithelial Cells.

PURPOSE: Our understanding of the respiratory health consequences of geogenic (earth-derived) particulate matter (PM) is limited. Recent in vivo evidence suggests that the concentration of iron is associated with the magnitude of the respiratory response to geogenic PM. We investigated the inflammatory and cytotoxic potential of silica and iron oxide particles alone, and in combination, on lung epithelial cells. METHODS: Bronchial epithelial cells (BEAS-2B) were exposed to silica (quartz, cristobalite) and/or iron oxide (hematite, magnetite) particles. Cytotoxicity and cytokine production (IL-6, IL-8, IL-1ß and TNF-α) were assessed by LDH assay and ELISA, respectively. In subsequent experiments, the cytotoxic and inflammatory potential of the particles was assessed using alveolar epithelial cells (A549). RESULTS: After 24 h of exposure, iron oxide did not cause significant cytotoxicity or production of cytokines, nor did it augment the response of silica in the BEAS2-B cells. In contrast, while the silica response was not augmented in the A549 cells by the addition of iron oxide, iron oxide particles alone were sufficient to induce IL-8 production in these cells. There was no response detected for any of the outcomes at the 4 h time point, nor was there any evidence of IL-1ß or TNF-α production. CONCLUSIONS: While previous studies have suggested that iron may augment silica-induced inflammation, we saw no evidence of this in human epithelial cells. We found that alveolar epithelial cells produce pro-inflammatory cytokines in response to iron oxide particles, suggesting that previous in vivo observations are due to the alveolar response to these particles.

In utero cigarette smoke exposure impairs somatic and lung growth in BALB/c mice.

The aim of this study was to assess whether in utero tobacco smoke exposure alone affects early-life lung growth and development. Pregnant BALB/c mice were exposed to cigarette smoke from six cigarettes per day, or air, from day 8 to 20 of gestation. At 2 weeks of age, pups were weighed and had their lung volumes and lung mechanics measured. Pups born from mothers exposed to cigarette smoke (CS pups; n=17) were significantly lighter (6.76 ± 0.76 versus 7.72 ± 0.68 g) and had lower lung volumes (0.123 ± 0.02 versus 0.149 ± 0.02 mL) than control pups (n=20). Respiratory mechanics were adversely impacted by cigarette smoke exposure. CS pups had higher baseline airway resistance, tissue damping and tissue elastance. These differences were largely due to lower lung volumes. Both tissue damping and elastance were increased excessively in CS pups at high transrespiratory pressures, while other parameters were not affected. There were no histological differences between groups. In utero tobacco smoke exposure significantly affects growth and development in BALB/c mice. These impacts may partially explain the susceptibility of infants born to smoking mothers to early respiratory disease and chronic respiratory disease as adults.

Acute Influenza A infection induces bronchial hyper-responsiveness in mice.

This study aimed to determine whether the route of administration of methacholine (MCh) influenced the pattern of airway hyper-responsiveness (AHR) in mice. BALB/c mice were inoculated with a 50-microL volume containing 10(4.5)-pfu Influenza virus A/Mem/1/71(H3N1) or media. MCh responsiveness in vivo [inhaled (0.01-30 mg/mL), i.v. MCh (6-48 microg/min/kg)] and in vitro were measured at day 4 post-infection (D4) during acute lower respiratory infection (LRI) and following resolution of infection at day 20 (D20) using a low-frequency, forced oscillation technique. Inflammation was assessed in bronchoalveolar lavage fluid. Infected mice had pulmonary inflammation and heightened responsiveness to both inhaled (p<0.03) and intravenous (p<0.02) MCh on D4, but not on D20. In vitro responsiveness was not altered at either time point. Influenza A LRI results in AHR during acute infection associated with a marked inflammatory response and increased permeability of the alveolar-capillary barrier. These data suggest that intrinsic muscle properties are not altered but MCh has greater access to airway smooth muscle during acute infection.

Suppression of the asthmatic phenotype by ultraviolet B-induced, antigen-specific regulatory cells.

BACKGROUND: Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV-induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV-induced effects. OBJECTIVE: To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen-induced airway immunity in a murine asthma model, and to examine the mechanisms involved. METHODS: BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway-associated, asthma-like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA-specific proliferative responses and cytokine production by cells from the lung-draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB-induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA-sensitized mice were adoptively transferred into naïve BALB/c mice that were subsequently sensitized and challenged with OVA, or a non-specific antigen. RESULTS: UVB irradiation of skin significantly suppressed AHR to methacholine and OVA-specific responses in the LDLN and in the lung compartment. Reduced OVA-specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 x 10(6) LDLN cells from UVB irradiated, but not from non-irradiated, OVA-sensitized mice suggested that UVB-induced regulatory cells are responsible for many of the asthma-reducing effects of dorsal UVB exposure. CONCLUSION: UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.