| Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma. | |
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MedLine Citation:
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PMID: 21493781 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We identified a previously unrecognized component of airborne particulate matter (PM) formed in combustion and thermal processes, namely, environmentally persistent free radicals (EPFRs). The pulmonary health effects of EPFRs are currently unknown. In the present study, we used a model EPFR-containing pollutant-particle system referred to as MCP230. We evaluated the effects of MCP230 on the phenotype and function of bone marrow-derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. We also investigated the adjuvant role of MCP230 on airway inflammation in a mouse model of asthma. MCP230 decreased intracellular reduced glutathione (GSH) and the GSH/oxidized glutathione ratio in BMDCs, and up-regulated the expression of costimulatory molecules CD80 and CD86 on DCs. The maturation of DCs was blocked by inhibiting oxidative stress or the uptake of MCP230. BMDCs exposed to MCP230 increased their antigen-specific T-cell proliferation in vitro. In a model of asthma, exposure to MCP230 exacerbated pulmonary inflammation, which was attributed to the increase of neutrophils and macrophages but not eosinophils. This result correlated with an increase in Th17 cells and cytokines, compared with non-MCP230-treated but ovalbumin (OVA)-challenged mice. The percentage of Th2 cells was comparable between OVA and OVA + MCP230 mice. Our data demonstrate that combustion-generated, EPFR-containing PM directly induced the maturation of DCs in an uptake-dependent and oxidative stress-dependent manner. Furthermore, EPFR-containing PM induced a Th17-biased phenotype in lung, accompanied by significant pulmonary neutrophilia. Exposure to EPFR-containing PM may constitute an important and unrecognized risk factor in the exacerbation and development of a severe asthma phenotype in humans. |
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Authors:
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Pingli Wang; Paul Thevenot; Jordy Saravia; Terry Ahlert; Stephania A Cormier |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-04-14 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: 45 ISSN: 1535-4989 ISO Abbreviation: Am. J. Respir. Cell Mol. Biol. Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-02 Completed Date: 2011-12-22 Revised Date: 2012-01-23 |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: United States |
Other Details:
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Languages: eng Pagination: 977-83 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, 70112, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD80 / biosynthesis, immunology Antigens, CD86 / biosynthesis, immunology Asthma / immunology* CD4-Positive T-Lymphocytes / drug effects, immunology Cell Differentiation / drug effects, immunology Cells, Cultured Dendritic Cells / drug effects, immunology* Disease Models, Animal Female Free Radicals / adverse effects*, pharmacology Glutathione / immunology, metabolism Lung / drug effects, immunology Macrophages, Alveolar / drug effects, immunology Male Mice Mice, Inbred BALB C Mice, Transgenic Neutrophils / drug effects, microbiology Oxidative Stress / drug effects, immunology Particulate Matter / adverse effects*, chemistry, pharmacology Th17 Cells / drug effects, immunology* Th2 Cells / drug effects, immunology Up-Regulation / drug effects, immunology |
| Grant Support | |
ID/Acronym/Agency:
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5R01ES015050/ES/NIEHS NIH HHS; P42 ES013648-01A25852/ES/NIEHS NIH HHS; P42 ES013648-025852/ES/NIEHS NIH HHS; P42ES013648/ES/NIEHS NIH HHS; R01 ES015050-05/ES/NIEHS NIH HHS; R01 ES015050-06/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD80; 0/Antigens, CD86; 0/Free Radicals; 0/Particulate Matter; 70-18-8/Glutathione |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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