Document Detail

Treatment with Fms-like tyrosine kinase 3 ligand reverses lung dendritic cell immunoparalysis and ameliorates zymosan-induced secondary lung injury in mice.
MedLine Citation:
PMID:  23039886     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  170     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2013-03-18     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  156-66     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
Department of Pathology, the First Affiliated Hospital of General Hospital of PLA, 51 Fucheng Road, Beijing 100048, China.
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MeSH Terms
Antigens, CD / immunology
Body Weight / immunology
Dendritic Cells / drug effects,  immunology*
Interleukin-10 / immunology
Interleukin-12 / immunology
Lung / drug effects,  immunology*
Lung Injury / chemically induced,  drug therapy,  enzymology,  immunology*
Membrane Proteins / pharmacology*
Mice, Inbred BALB C
Multiple Organ Failure / immunology*
Survival Rate
Zymosan / pharmacology
fms-Like Tyrosine Kinase 3 / immunology*
Reg. No./Substance:
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 protein, mouse; EC Tyrosine Kinase 3

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