Journal Article

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

Ye, Yang, Jin, Sheng‐Wei, Mei, Hong‐Xia, Xiang, Shu‐Yang, Yang, Qian, Zheng, Sheng‐Xing, Wang, Qian, Xu, Hao‐Ran, Gao Smith, Fang, Zhang, Hua‐Wei

2020

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Acute Lung Injury - chemically induced / Acute Lung Injury - pathology / acute respiratory distress syndrome / Administration, Intranasal / Animals / Bisphosphonates / Chemokine CCL2 - biosynthesis / Chemokine CCL2 - genetics / Chemokine CXCL2 - biosynthesis / Chemokine CXCL2 - genetics / Chemokine CXCL2 - physiology / Chemokine receptors / Chemokines / Chemotaxis, Leukocyte - drug effects / Clodronic acid / Clodronic Acid - administration & dosage / Clodronic Acid - pharmacology / Cytokines / Docosahexaenoic Acids - pharmacology / Docosahexaenoic Acids - physiology / Docosahexaenoic Acids - therapeutic use / Flow cytometry / Gelatinase B / Gene expression / Infiltration / Inflammation / Injections, Intraperitoneal / Laboratory animals / Leukocytes (neutrophilic) / Lipopolysaccharides / Lipopolysaccharides - administration & dosage / Lipopolysaccharides - toxicity / Liposomes / Lungs / Macrophage inflammatory protein / Macrophages / Macrophages - drug effects / Macrophages - physiology / Matrix Metalloproteinase 9 - physiology / Mice / Mice, Inbred C57BL / Monocyte chemoattractant protein 1 / neutrophil / Neutrophils / Neutrophils - drug effects / Original / protectin DX / Receptors, CCR2 - antagonists & inhibitors / Receptors, Interleukin-8B - antagonists & inhibitors / recruited macrophage / Recruitment / resident macrophage / Respiratory distress syndrome / Signal transduction / Signal Transduction - drug effects / Software / Trachea / Transendothelial and Transepithelial Migration - drug effects / Tumor necrosis factor / Tumor Necrosis Factor-alpha - physiology / Tumor necrosis factor-α