1. Academic Validation
  2. PDX regulates inflammatory cell infiltration via resident macrophage in LPS-induced lung injury

PDX regulates inflammatory cell infiltration via resident macrophage in LPS-induced lung injury

  • J Cell Mol Med. 2020 Sep;24(18):10604-10614. doi: 10.1111/jcmm.15679.
Yang Ye 1 Hua-Wei Zhang 1 Hong-Xia Mei 1 Hao-Ran Xu 1 Shu-Yang Xiang 1 Qian Yang 1 Sheng-Xing Zheng 1 Fang Gao Smith 1 2 Sheng-Wei Jin 1 Qian Wang 1
Affiliations

Affiliations

  • 1 Department of Anesthesia and Critical Care, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.
  • 2 Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Abstract

Inflammatory cell infiltration contributes to the pathogenesis of acute respiratory distress syndrome (ARDS). Protectin DX (PDX), an endogenous lipid mediator, shows anti-inflammatory and proresolution bioactions. In vivo, the mice were intraperitoneally injected with PDX (0.1 µg/mouse) after intratracheal (1 mg/kg) or intraperitoneal (10 mg/kg) LPS administration. Flow cytometry was used to measure inflammatory cell numbers. Clodronate liposomes were used to deplete resident macrophages. RT-PCR, and ELISA was used to measure MIP-2, MCP-1, TNF-α and MMP9 levels. In vitro, sorted neutrophils, resident and recruited macrophages (1 × 106 ) were cultured with 1 μg/mL LPS and/or 100 nmol/L PDX to assess the Chemokine Receptor expression. PDX attenuated LPS-induced lung injury via inhibiting recruited macrophage and neutrophil recruitment through repressing resident macrophage MCP-1, MIP-2 expression and release, respectively. Finally, PDX inhibition of neutrophil infiltration and transmembrane was associated with TNF-α/MIP-2/MMP9 signalling pathway. These data suggest that PDX attenuates LPS-stimulated lung injury via reduction of the inflammatory cell recruitment mediated via resident macrophages.

Keywords

acute respiratory distress syndrome; neutrophil; protectin DX; recruited macrophage; resident macrophage.

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