Respiratory infections cause the release of extracellular vesicles: implications in exacerbation of asthma/COPD
Autor: | Eltom, S, Dale, N, Raemdonck, KRG, Stevenson, CS, Snelgrove, RJ, Sacitharan, PK, Recchi, C, Wavre-Shapton, S, McAuley, DF, O'Kane, C, Belvisi, MG, Birrell, MA, Chan, RWY |
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Přispěvatelé: | Chan, R, Medical Research Council (MRC) |
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Lipopolysaccharides
Male Pulmonology SMOKE Respiratory System Interleukin-1beta lcsh:Medicine Mice Pulmonary Disease Chronic Obstructive Adenosine Triphosphate Cell-Derived Microparticles Medicine and Health Sciences P2X7 RECEPTOR Medicine Respiratory system lcsh:Science Immune Response Respiratory Tract Infections COPD Multidisciplinary Respiratory tract infections Respiratory disease Interleukin-18 Extracellular vesicle INDUCED LUNG INJURY Caspases Science & Technology - Other Topics SECRETION medicine.symptom Anatomy Research Article General Science & Technology Immunology Caspase 1 Inflammation NANOPARTICLE TRACKING ANALYSIS OBSTRUCTIVE PULMONARY-DISEASE DENDRITIC CELLS SDG 3 - Good Health and Well-being Cell Line Tumor MD Multidisciplinary Animals Humans Science & Technology MULTIDISCIPLINARY SCIENCES business.industry lcsh:R Immunity Biology and Life Sciences GLOBAL BURDEN medicine.disease Neutrophilia Asthma Mice Inbred C57BL Respiratory Infections lcsh:Q Receptors Purinergic P2X7 business INDUCED AIRWAY INFLAMMATION |
Zdroj: | PLoS ONE, Vol 9, Iss 6, p e101087 (2014) PLoS ONE Eltom, S, Dale, N, Raemdonck, K R G, Stevenson, C S, Snelgrove, R J, Sacitharan, P K, Recchi, C, Wavre-Shapton, S, McAuley, D F, O'Kane, C, Belvisi, M G & Birrell, M A 2014, ' Respiratory Infections Cause the Release of Extracellular Vesicles: Implications in Exacerbation of Asthma/COPD ', PloS one, vol. 9, no. 6, e101087 . https://doi.org/10.1371/journal.pone.0101087 |
ISSN: | 1932-6203 |
Popis: | Background Infection-related exacerbations of respiratory diseases are a major health concern; thus understanding the mechanisms driving them is of paramount importance. Despite distinct inflammatory profiles and pathological differences, asthma and COPD share a common clinical facet: raised airway ATP levels. Furthermore, evidence is growing to suggest that infective agents can cause the release of extracellular vesicle (EVs) in vitro and in bodily fluids. ATP can evoke the P2X7/caspase 1 dependent release of IL-1b/IL-18 from EVs; these cytokines are associated with neutrophilia and are increasedduring exacerbations. Thus we hypothesized that respiratory infections causes the release of EVs in the airway and that theraised ATP levels, present in respiratory disease, triggers the release of IL-1b/IL-18, neutrophilia and subsequent diseaseexacerbations. Methods To begin to test this hypothesis we utilised human cell-based assays,ex vivomurine BALF,in vivo pre-clinical models and human samples to test this hypothesis. Results Data showed that in a murine model of COPD, known to have increased airway ATP levels, infective challenge causes exacerbated inflammation. Using cell-based systems, murine models and samples collected from challenged healthy subjects, we showed that infection can trigger the release of EVs. When exposed to ATP the EVs release IL-1b/IL-18 via a P2X7/caspase-dependent mechanism. Furthermore ATP challenge can cause a P2X7 dependent increase in LPS-driven neutrophilia. Conclusions This preliminary data suggests a possible mechanism for how infections could exacerbate respiratory diseases and may highlight a possible signalling pathway for drug discovery efforts in this area. |
Databáze: | OpenAIRE |
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