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dc.contributor.authorCho, W-S
dc.contributor.authorDuffin, R
dc.contributor.authorHowie, SEM
dc.contributor.authorScotton, CJ
dc.contributor.authorWallace, WAH
dc.contributor.authorMacnee, W
dc.contributor.authorBradley, M
dc.contributor.authorMegson, IL
dc.contributor.authorDonaldson, K
dc.date.accessioned2017-05-09T10:10:42Z
dc.date.issued2011-09-06
dc.description.abstractBACKGROUND: Large production volumes of zinc oxide nanoparticles (ZnONP) might be anticipated to pose risks, of accidental inhalation in occupational and even in consumer settings. Herein, we further investigated the pathological changes induced by ZnONP and their possible mechanism of action. METHODS: Two doses of ZnONP (50 and 150 cm2/rat) were intratracheally instilled into the lungs of rats with assessments made at 24 h, 1 wk, and 4 wks after instillation to evaluate dose- and time-course responses. Assessments included bronchoalveolar lavage (BAL) fluid analysis, histological analysis, transmission electron microscopy, and IgE and IgA measurement in the serum and BAL fluid. To evaluate the mechanism, alternative ZnONP, ZnONP-free bronchoalveolar lavage exudate, and dissolved Zn2+ (92.5 μg/rat) were also instilled to rats. Acridine orange staining was utilized in macrophages in culture to evaluate the lysosomal membrane destabilization by NP. RESULTS: ZnONP induced eosinophilia, proliferation of airway epithelial cells, goblet cell hyperplasia, and pulmonary fibrosis. Bronchocentric interstitial pulmonary fibrosis at the chronic phase was associated with increased myofibroblast accumulation and transforming growth factor-β positivity. Serum IgE levels were up-regulated by ZnONP along with the eosinophilia whilst serum IgA levels were down-regulated by ZnONP. ZnONP are rapidly dissolved under acidic conditions (pH 4.5) whilst they remained intact around neutrality (pH 7.4). The instillation of dissolved Zn2+ into rat lungs showed similar pathologies (eg., eosinophilia, bronchocentric interstitial fibrosis) as were elicited by ZnONP. Lysosomal stability was decreased and cell death resulted following treatment of macrophages with ZnONP in vitro. CONCLUSIONS: We hypothesise that rapid, pH-dependent dissolution of ZnONP inside of phagosomes is the main cause of ZnONP-induced diverse progressive severe lung injuries.en_GB
dc.description.sponsorshipFinancial support was provided by the Medical Research Council of United Kingdom (MRC G0701323). CJS is supported by MRC Career Development Award (G0800340). KD acknowledges the support of the Colt Foundation.en_GB
dc.identifier.citationVol. 8, pp. 27 -en_GB
dc.identifier.doi10.1186/1743-8977-8-27
dc.identifier.other1743-8977-8-27
dc.identifier.urihttp://hdl.handle.net/10871/27440
dc.language.isoenen_GB
dc.publisherBioMed Centralen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/21896169en_GB
dc.rights© Cho et al; licensee BioMed Central Ltd. 2011en_GB
dc.subjectAnimalsen_GB
dc.subjectBronchoalveolar Lavage Fluiden_GB
dc.subjectCytokinesen_GB
dc.subjectDisease Progressionen_GB
dc.subjectEnzyme-Linked Immunosorbent Assayen_GB
dc.subjectFemaleen_GB
dc.subjectImmunoglobulin Aen_GB
dc.subjectImmunoglobulin Een_GB
dc.subjectImmunohistochemistryen_GB
dc.subjectInhalation Exposureen_GB
dc.subjectLungen_GB
dc.subjectLung Injuryen_GB
dc.subjectLysosomesen_GB
dc.subjectMiceen_GB
dc.subjectMice, Inbred BALB Cen_GB
dc.subjectMice, Inbred C57BLen_GB
dc.subjectMicroscopy, Electron, Transmissionen_GB
dc.subjectNanoparticlesen_GB
dc.subjectParticle Sizeen_GB
dc.subjectRatsen_GB
dc.subjectRats, Wistaren_GB
dc.subjectSeverity of Illness Indexen_GB
dc.subjectSolubilityen_GB
dc.subjectSurface Propertiesen_GB
dc.subjectZinc Oxideen_GB
dc.titleProgressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+ dissolution inside lysosomes.en_GB
dc.typeArticleen_GB
dc.date.available2017-05-09T10:10:42Z
exeter.place-of-publicationEnglanden_GB
dc.descriptionPublished onlineen_GB
dc.descriptionJournal Articleen_GB
dc.descriptionResearch Support, Non-U.S. Gov'ten_GB
dc.descriptionThis is the final version of the article. Available from BioMed Central via the DOI in this record.en_GB
dc.identifier.eissn1743-8977
dc.identifier.journalParticle and Fibre Toxicologyen_GB


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