Treatment with Fms-like tyrosine kinase 3 ligand reverses lung dendritic cell immunoparalysis and ameliorates zymosan-induced secondary lung injury in mice.

Abstract

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.

• Authors: H W Wang, W Yang, J Y Lu, G Tian, F Li, X H Wang, J R Kang, Y Yang
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 170 Issue 2 Pg. 156-66 (Nov 2012) ISSN: 1365-2249 [Electronic] England
• PMID: 23039886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 British Society for Immunology.

Chemical References

• Antigens, CD
• Ligands
• Membrane Proteins
• flt3 ligand protein
• Interleukin-10
• Interleukin-12
• Zymosan
• Flt3 protein, mouse
• fms-Like Tyrosine Kinase 3

Topics

• 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)