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| 2. |
- Bosson, Jenny, et al.
(författare)
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Ozone-induced bronchial epithelial cytokine expression differs between healthy and asthmatic subjects
- 2003
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 33:6, s. 777-782
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Tidskriftsartikel (refereegranskat)abstract
- Background Ozone (O3) is a common air pollutant associated with adverse health effects. Asthmatics have been suggested to be a particularly sensitive group. Objective This study evaluated whether bronchial epithelial cytokine expression would differ between healthy and allergic asthmatics after ozone exposure, representing an explanatory model for differences in susceptibility. Methods Healthy and mild allergic asthmatic subjects (using only inhaled β2-agonists prn) were exposed for 2 h in blinded and randomized sequence to 0.2 ppm of O3 and filtered air. Bronchoscopy with bronchial mucosal biopsies was performed 6 h after exposure. Biopsies were embedded in GMA and stained with mAbs for epithelial expression of IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, GRO-α, granulocyte–macrophage colony-stimulating factor (GM–CSF), fractalkine and ENA-78. Results When comparing the two groups at baseline, the asthmatic subjects showed a significantly higher expression of IL-4 and IL-5. After O3 exposure the epithelial expression of IL-5, GM–CSF, ENA-78 and IL-8 increased significantly in asthmatics, as compared to healthy subjects. Conclusion The present study confirms a difference in epithelial cytokine expression between mild atopic asthmatics and healthy controls, as well as a differential epithelial cytokine response to O3. This O3-induced upregulation of T helper type 2 (Th2)-related cytokines and neutrophil chemoattractants shown in the asthmatic group may contribute to a subsequent worsening of the airway inflammation, and help to explain their differential sensitivity to O3 pollution episodes.
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| 3. |
- Eriksson Ström, Jonas, et al.
(författare)
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Airway regulatory T cells are decreased in COPD with a rapid decline in lung function
- 2020
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Ingår i: Respiratory Research. - : BioMed Central. - 1465-9921 .- 1465-993X. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in the expression of regulatory T cells (Tregs) have been suggested to explain why some smokers develop COPD and some do not. Upregulation of Tregs in response to smoking would restrain airway inflammation and thus the development of COPD; while the absense of such upregulation would over time lead to chronic inflammation and COPD. We hypothesized that—among COPD patients—the same mechanism would affect rate of decline in lung function; specifically, that a decreased expression of Tregs would be associated with a more rapid decline in FEV1.Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.Results: The proportions of Tregs with regulatory function (FoxP3+/CD4+CD25bright) were significantly lower in COPD subjects with a rapid decline in lung function compared to those with a non-rapid decline (p = 0.019). This result was confirmed in a mixed model regression analysis in which adjustments for inhaled corticosteroid usage, smoking, sex and age were evaluated. No significant difference was found between COPD subjects and smokers or non-smokers with normal lung function.Conclusions: COPD subjects with a rapid decline in lung function had lower proportions of T cells with regulatory function in BAL fluid, suggesting that an inability to suppress the inflammatory response following smoking might lead to a more rapid decline in FEV1.
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| 4. |
- Eriksson Ström, Jonas, et al.
(författare)
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Cytotoxic lymphocytes in COPD airways : increased NK cells associated with disease, iNKT and NKT-like cells with current smoking
- 2018
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Ingår i: Respiratory Research. - : BMC. - 1465-9921 .- 1465-993X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytotoxic lymphocytes are increased in the airways of COPD patients. Whether this increase is driven primarily by the disease or by smoking is not clear, nor whether it correlates with the rate of decline in lung function.Methods: Bronchoscopy with BAL was performed in 52 subjects recruited from the longitudinal OLIN COPD study according to pre-determined criteria; 12 with COPD and a rapid decline in lung function (loss of FEV1 ≥ 60 ml/year), 10 with COPD and a non-rapid decline in lung function (loss of FEV1 ≤ 30 ml/year), 15 current and ex-smokers and 15 non-smokers with normal lung function. BAL lymphocyte subsets were determined using flow cytometry.Results: In BAL fluid, the proportions of NK, iNKT and NKT-like cells all increased with pack-years. Within the COPD group, NK cells – but not iNKT or NKT-like cells – were significantly elevated also in subjects that had quit smoking. In contrast, current smoking was associated with a marked increase in iNKT and NKT-like cells but not in NK cells. Rate of lung function decline did not significantly affect any of the results.Conclusions: In summary, increased proportions of NK cells in BAL fluid were associated with COPD; iNKT and NKT-like cells with current smoking but not with COPD. Interestingly, NK cell percentages did not normalize in COPD subjects that had quit smoking, indicating that these cells might play a role in the continued disease progression seen in COPD even after smoking cessation.Trial registration: Clinicaltrials.gov identifier NCT02729220.
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| 6. |
- Gustafsson, Åsa, et al.
(författare)
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Mice with established airway inflammation exert differential cellular responses to inhaled hematite nanoparticles than healthy mice
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to investigate the inflammatory and immunological responses in the airways and the lung-draining lymph nodes, following lung exposure to hematite nanoparticles (NPs). The responses to hematite NPs were evaluated in both non-sensitized healthy mice, and allergen-sensitized mice, in which the latter represent a group of sensitive individuals with allergic airway disease. This allergic airway disease was induced by sensitization and aerosol challenge to a respiratory allergen resulting in an established eosinophilic and lymphocytic airway inflammation at the time of NP exposure. The mice received either hematite NPs or vehicle (PBS) intratracheally and the cellular responses were evaluated on day 1, 2, and 7, following exposure.Intratracheal instillation of hematite NPs induced an increase of neutrophils, eosinophils, and lymphocytes in the airways of non-sensitized mice on day 1 and 2 following exposure. At these time-points the lymphocytes in the lymph nodes were also increased. In contrast, exposure to hematite NPs in sensitized mice induced a rapid and unspecific cellular reduction in the alveolar space on the first day after exposure. A similar decrease of lymphocytes was also observed in the mediastinal lymph nodes draining the airways. The study did not indicate a reduction of inflammatory cells in the lung tissue or a translocation of cells from alveolar space to lung tissue. Although, mucociliary cellular clearance could be a possible explanation, our finding of cellular decrease also in lung draining lymph nodes point at cell death as the most likely cause to this unspecific cellular reduction.The results indicate that cells in the airways and lymph nodes of individuals with established airway inflammation undergo cell death when exposed to iron oxide NPs. A possible reason to the toxic response is extensive generation of reactive oxygen species (ROS) in the pro-oxidative environment of inflamed airways, which is further catalyzed by Fe ions released by the hematite NPs, or by generation of ROS at the surface of the NPs. Such cell toxic response was not detected in healthy non-sensitized individuals. This study clearly demonstrates the different response of sensitized and non-sensitized mice, and highlights the importance of including individuals with respiratory disorders, such as allergic asthma, when evaluating health effects of inhaled nanomaterials.
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| 7. |
- Löfdahl, Magnus J, et al.
(författare)
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Increased intraepithelial T-cells in stable COPD
- 2008
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 102:12, s. 1812-1818
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The airway epithelium is the first line of defence in the response to inhaled particles and irritants. Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by an irreversible loss of lung function, with cigarette smoking as a major risk factor. Here, we address intraepithelial T-cells in COPD, as these cells are a distinct T-cell subtype thought to have important regulatory functions. We hypothesised that intraepithelial T-cells play a role in the response to lung irritants and that the T-cell populations would be altered and associated with signs of inflammation in COPD. METHODS: Bronchoscopy with endobronchial mucosal biopsy sampling was performed in 22 patients (mean age; 57) with stable COPD (median FEV(1)% predicted: 51). Age- and smoking- matched smokers (S) with normal lung function (n=14) and age-matched non-smokers (NS) (n=15) served as controls. Airway inflammation was recorded visually using bronchitis index (BI). Biopsy specimens were processed into glycol methacrylate resin and inflammatory cells were stained immunohistochemically. RESULTS: The number of intraepithelial CD4+ T-cells were significantly higher in COPD patients compared to smokers as well as trend towards significance in non-smokers (p=0.005 and p=0.036, respectively), whereas intraepithelial CD8+ T-cells number were increased in patients with COPD compared to non-smokers (p=0.017). Both patients with COPD and smokers had a higher BI than non-smokers (p<0.001 for both). CONCLUSIONS: The present data suggest a role for intraepithelial CD4+ and CD8+ T-cells in stable COPD and indicate that T-cells are of importance in the long-term inflammatory response in COPD or, alternatively, play a regulatory role.
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| 8. |
- Muala, Ala, et al.
(författare)
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Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers
- 2014
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure 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.METHODS: Thirty 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.RESULTS: The 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.CONCLUSIONS: A 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.
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| 9. |
- Roos-Engstrand, Ester, 1962-, et al.
(författare)
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Cytotoxic T cells expressing the co-stimulatory receptor NKG2D are increased in cigarette smoking and COPD
- 2010
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 11, s. 128-
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Tidskriftsartikel (refereegranskat)abstract
- Background: A suggested role for T cells in COPD pathogenesis is based on associations between increased lung cytotoxic T lymphocyte (CD8+) numbers and airflow limitation. CD69 is an early T cell activation marker. NKG2D receptors are co-stimulatory molecules induced on CD8+ T cells upon activation. The activating function of NKG2D is triggered by binding to the MHC class 1 chain-related (MIC) molecules A and B, expressed on surface of stressed epithelial cells. The aim of this study was to evaluate the expression of MIC A and B in the bronchial epithelium and NKG2D and CD69 on BAL lymphocytes in subjects with COPD, compared to smokers with normal lung function and healthy never-smokers.Methods: Bronchoscopy with airway lavages and endobronchial mucosal biopsy sampling was performed in 35 patients with COPD, 21 healthy never-smokers and 16 smokers with normal lung function. Biopsies were immunohistochemically stained and BAL lymphocyte subsets were determined using flow cytometry. Results: Epithelial CD3+ lymphocytes were increased in both smokers with normal lung function and in COPD patients, compared to never-smokers. Epithelial CD8+ lymphocyte numbers were higher in the COPD group compared to never-smoking controls. Among gated CD3+cells, the percentage of CD8+ NKG2D+ cells was enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers. The percentage of CD8+ CD69+ cells and cell surface expression of CD69 were enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers. No changes in the expression of MIC A or MIC B in the airway epithelium could be detected between the groups, whereas significantly decreased soluble MICB was detected in bronchial wash from smokers with normal lung function, compared to never-smokers.Conclusions: In COPD, we found increased numbers of cytotoxic T cells in both bronchial epithelium and airway lumen. Further, the proportions of CD69- and NKG2D-expressing cytotoxic T cells in BAL fluid were enhanced in both subjects with COPD and smokers with normal lung function and increased expression of CD69 was found on CD8+ cells, indicating the cigarette smoke exposure-induced expansion of activated cytotoxic T cells, which potentially can respond to stressed epithelial cells.
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| 10. |
- Roos-Engstrand, Ester, et al.
(författare)
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Expansion of CD4+CD25+ helper T cells without regulatory function in smoking and COPD
- 2011
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Ingår i: Respiratory Research. - London : BioMed Central. - 1465-9921 .- 1465-993X. ; 12:74, s. 8-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.Method: Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.Results: In smokers with normal lung function, the expression of CD25+CD4+ was increased, whereas the proportions of FoxP3+ and CD127+ were unchanged compared to never-smokers. Among CD4+cells expressing high levels of CD25, the proportion of FoxP3+ cells was decreased and the percentage of CD127+ was increased in smokers with normal lung function. CD4+CD25+ cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.Conclusion: The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25+ helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development.
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