Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome

Li,Lang; Dong,Liang; Zhao,Dan; Gao,Fei; Yan,Jie

doi:10.3892/ijmm.2019.4208

Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome

Authors:
- Lang Li
- Liang Dong
- Dan Zhao
- Fei Gao
- Jie Yan
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Affiliations: Department of Critical Care Medicine, Taizhou Central Hospital, Taizhou University Hospital, Taizhou, Zhejiang 318000, P.R. China, Department of Critical Care Medicine, Wuxi People's Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
Published online on: May 23, 2019 https://doi.org/10.3892/ijmm.2019.4208
Pages: 617-629
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Classical dendritic cells (cDCs) are involved in the pathogenesis of inflammatory lung diseases; however, their contributions in acute respiratory distress syndrome (ARDS), which is pathophysiologically inflammatory, remain unknown. The present study aimed to explore the regulatory effects of pulmonary cDCs on acute lung inflammation and injury in lipopolysaccharide (LPS)‑induced ARDS. Fms‑like tyrosine kinase 3‑ligand (FLT3L) and lestaurtinib, a specific activator and an inhibitor of FLT3 signaling respectively, were used separately for the pretreatment of C57BL/6 mice for 5 consecutive days. ARDS was induced by intratracheal injection of LPS, and mice were sacrificed 6 and 24 h later. Flow cytometry was used to measure the aggregation and maturation of pulmonary cDCs. The ratio of lung wet weight to body weight (LWW/BW) and histopathological analyses were assessed to evaluate lung edema and lung injury. Tumor necrosis factor‑α and interleukin (IL)‑6 levels were measured by ELISA to evaluate acute lung inflammation. The levels of interferon‑γ, IL‑1β, IL‑4 and IL‑10, and the expression of the transcription factors T‑box‑expressed‑in‑T‑cells (T‑bet) and GATA binding protein 3, were quantified by ELISA, RT‑qPCR and western blotting to evaluate the balance of the Th1/Th2 response. Myeloperoxidase (MPO) activity was measured to evaluate neutrophil infiltration. The results demonstrated that the aggregation and maturation of pulmonary cDCs reached a peak at 6 h after LPS challenge, followed by a significant decrease at 24 h. FLT3L pretreatment further stimulated the aggregation and maturation of pulmonary cDCs, resulting in elevated lung MPO activity and increased T‑bet expression, which in turn led to aggravated LWW/BW, acute lung inflammation and injury. However, lestaurtinib pretreatment inhibited the aggregation and maturation of pulmonary cDCs, decreased lung MPO activity and T‑bet expression, and eventually improved LWW/BW, acute lung inflammation and injury. The present results suggested that pulmonary cDCs regulated acute lung inflammation and injury in LPS‑induced ARDS through the modulation of neutrophil infiltration and balance of the Th1/Th2 response.

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