Classical dendritic cells regulate acute lung inflammation and injury in mice with lipopolysaccharide‑induced acute respiratory distress syndrome
Open Access
- 23 May 2019
- journal article
- research article
- Published by Spandidos Publications in International Journal of Molecular Medicine
- Vol. 44 (2), 617-629
- https://doi.org/10.3892/ijmm.2019.4208
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.Keywords
This publication has 48 references indexed in Scilit:
- FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivoBlood, 2011
- Plasmacytoid Dendritic Cells Control Lung Inflammation and Monocyte Recruitment in Indirect Acute Lung Injury in MiceThe American Journal of Pathology, 2010
- FMS-LIKE TYROSINE KINASE-3 LIGAND ALTERS ANTIGEN-SPECIFIC RESPONSES TO INFECTIONS AFTER SEVERE BURN INJURYShock, 2009
- Fms-like tyrosine kinase 3 ligand increases a lung DC subset with regulatory properties in allergic airway inflammationJournal of Allergy and Clinical Immunology, 2009
- The Balance between Plasmacytoid DC versus Conventional DC Determines Pulmonary Immunity to Virus InfectionsPLOS ONE, 2008
- Conventional dendritic cells regulate the outcome of colonic inflammation independently of T cellsProceedings of the National Academy of Sciences of the United States of America, 2007
- Two way communication between neutrophils and dendritic cellsCurrent Opinion in Pharmacology, 2006
- Severe Sepsis Exacerbates Cell-Mediated Immunity in the Lung Due to an Altered Dendritic Cell Cytokine ProfileThe American Journal of Pathology, 2006
- Accurate and simple discrimination of mouse pulmonary dendritic cell and macrophage populations by flow cytometry: Methodology and new insightsCytometry Part A, 2004
- The B7–CD28 superfamilyNature Reviews Immunology, 2002