The control effects of FLT3 signaling-dependent pulmonary conventional dendritic ceils on the initiation of acute lung inflammation response to lipopolysaccharide induced acute lung injury in mice
10.3760/cma.j.issn.1671-0282.2016.11.012
- VernacularTitle:FLT3信号通路介导常规树突状细胞启动和调节急性肺损伤早期炎症反应的机制研究
- Author:
Liang DONG
;
Hongli HE
;
Jun LIU
;
Ling LIU
;
Yi YANG
;
Haibo QIU
- Keywords:
Acute lung injury;
Conventional dendritic cells;
FLT3 signaling;
Inflammation;
Neutrophils infiltration;
T-helper-cell response;
Pathogenesis
- From:
Chinese Journal of Emergency Medicine
2016;25(11):1412-1417
- CountryChina
- Language:Chinese
-
Abstract:
Objective To clarify the role of FLT3 signaling-dependent pulmonary conventional dendritic cells (cDCs) in the pathogenesis of lipopolysaccharide (LPS)-induced acute lung injury (ALI),and as well as the modulation effects of cDCs in vivo on the inflammatory responses to acute lung injury.Methods Thirty C57BL/6 male mice were divided into normal control group,LPS group,FLT3L pretreatment group,lestaurtinib,(a high efficient and specific blocker in FLT3 signal pathway) pretreatment group and vehicle (DMSD) control group.FLT3L and lestaurtinib were administrated subcutaneously for 5 days.Murine model of ALI was subsequently established by intra-tracheal application of LPS and lung specimens were harvested 6 h or 24 h later.The accumulation and maturation of pulmonary cDCs were assessed by flow cytometry.IL-6 and TNF-α were quantified to evaluate lung inflammation.Lung injury was estimated by lung wet weight/body weight ratio (LWW/BW) and histopathological assessment.Lung myeloperoxidase (MPO) activity was measured to evaluate neutrophil infiltration.Transcription factors Tbet/GATA-3 mRNA ratio was determined to estimate balance of Th1/Th2 response.IFN-γ and IL-4 were quantified to evaluate Th1-specific and Th2-specific cytokine production respectively.Results The accumulation and maturation of pulmonary cDCs peaked at 6h after LPS challenge.FLT3L pretreatment significantly stimulated the accumulation and maturation of pulmonary cDCs (P ＜ 0.05),leading to markedly deterioration of LWW/BW and lung histopathological changes.Meanwhile lung MPO activity and T-bet/GATA-3 mRNA ratio were elevated (P ＜ 0.05).Furthermore,the production of IL-6,TNF-α and IFN-γwas markedly increased by FLT3L pretreatment (P ＜ 0.05).In contrast,lestaurtinib pretreatment markedly inhibited the accumulation and maturation of pulmonary cDCs (P ＜ 0.05),leading to significant improvement of LWW/BW and lung histopathological changes.Meanwhile lung MPO activity and T-bet/ GATA-3 mRNA ratio were decreased (P ＜ 0.05).Furthermore lestaurtinib efficiently suppressed the production of IL-6,TNF-α and IFN-γ (P ＜ 0.05).Conclusion This study thus demonstrated that FLT3 signaling-dependent pulmonary cDCs could control the initiation of acute lung inflammation response to LPS-induced ALI through the regulation of neutrophil infiltration and balance of Thl/Th2 response.
