| Treatment with Fms-like tyrosine kinase 3 ligand reverses lung dendritic cell immunoparalysis and ameliorates zymosan-induced secondary lung injury in mice. | |
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MedLine Citation:
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PMID: 23039886 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Depletion and dysfunction of dendritic cells in the lung can induce local immunoparalysis, which often leads to multiple organ dysfunction syndrome (MODS)-associated mortality. A therapeutic strategy that reverses this immunoparalysis is required. In the present study, we examined the effects of in vivo Fms-like tyrosine kinase 3 ligand (Flt3L) treatment on zymosan (zym)-induced secondary lung injury and dendritic cell (DC) immunoparalysis. BALBc mice were divided randomly into four groups (20/group): (1) sham [intraperitoneal (i.p.) saline] + vehicle [subcutaneous (s.c.) 0·01% mouse serum albumin]; (2) sham + Flt3L (s.c.); (3) zym (i.p.) + vehicle; and (4) zym + Flt3L. Injections were for 9 consecutive days; 12 days later we examined: survival rate (monitored for 12 days); lung tissue histopathology (haematoxylin and eosin staining); plasma indices of lung function (pH, PaO(2) , PaCO(2) , HCO(3) (-) ); DC subsets in lung tissue; and lung DCs production of interleukin (IL)-12p70 and IL-10. Zym administration resulted in increased mortality associated with significant lung histopathological changes and abnormal blood gas indices; however, these pathological changes were ameliorated by Flt3L treatment. Zym injections also resulted in significant reductions in DC subsets recovered from lungs [CD11c(+) major histocompatibility complex (MHC)-II/I-A(d+) , CD11c(+) CD11b(+) and CD11c(+) B220(+) ]. Importantly, in-vivo Flt3L treatment reversed these trends for DC immunoparalysis by increasing the percentages of recovered DC subsets concomitant with increased DC production of IL-12 p70 and decreased IL-10 production. These results suggest that Flt3L may have therapeutic potential for reversing DC immunoparalysis and ameliorating lung injury secondary to MODS. |
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Authors:
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H W Wang; W Yang; J Y Lu; G Tian; F Li; X H Wang; J R Kang; Y Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 170 ISSN: 1365-2249 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-08 Completed Date: 2013-03-18 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 156-66 Citation Subset: IM |
Copyright Information:
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© 2012 British Society for Immunology. |
Affiliation:
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Department of Pathology, the First Affiliated Hospital of General Hospital of PLA, 51 Fucheng Road, Beijing 100048, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD / immunology Body Weight / immunology Dendritic Cells / drug effects, immunology* Interleukin-10 / immunology Interleukin-12 / immunology Ligands Lung / drug effects, immunology* Lung Injury / chemically induced, drug therapy, enzymology, immunology* Male Membrane Proteins / pharmacology* Mice Mice, Inbred BALB C Multiple Organ Failure / immunology* Survival Rate Zymosan / pharmacology fms-Like Tyrosine Kinase 3 / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Ligands; 0/Membrane Proteins; 0/flt3 ligand protein; 130068-27-8/Interleukin-10; 187348-17-0/Interleukin-12; 9010-72-4/Zymosan; EC 2.7.10.1/Flt3 protein, mouse; EC 2.7.10.1/fms-Like Tyrosine Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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