• Chaofeng Zhang, Shanshan Hu, Graeme R Zosky, Xin Wei, Shuhua Shu, Di Wang, and Xiaoqing Chai.
• Department of Anesthesiology, First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
• Shock. 2021 Feb 1; 55 (2): 236243236-243.

ObjectiveLung-recruited Ly6Chi monocytes had been shown to be involved in ventilator-induced lung injury (VILI). Our present study aimed to investigate whether the cyclooxygenase-2 (COX-2) inhibition modulates the function of lung-recruited Ly6Chi monocytes in a mouse model of VILI.MethodsMice were exposed to lipopolysaccharide (LPS; 20 ng) intraperitoneally prior to injurious mechanical ventilation (Vt = 30 mL/kg, PEEP = 0 cmH2O). A subgroup of mice was treated with intravenous parecoxib (30 mg/kg), a COX-2 inhibitor, 1 h prior to ventilation. Control mice received saline and were not ventilated. At the end of the experiment, blood gas analysis was performed and lung tissue was collected for histological assessment. Flow cytometry was employed to quantify the different populations of lung monocytes/macrophages and their function. Isolated Ly6Chi cells were used to measure the intracellular concentrations of reactive oxygen species (ROS) and nitric oxide (NO) by fluorescent probes, and cytokine production by cytometric bead array.ResultsExposure to LPS and injurious ventilation was associated with severe lung histological damage, oxygenation impairment, and pulmonary edema; all of which were largely attenuated following the treatment of parecoxib. Furthermore, flow cytometry analysis revealed that parecoxib caused a reduction in the number of the lung-recruited CD11bloLy6Chi monocytes while there was no effect on tissue-resident CD64+ alveolar macrophages. In addition, the production of oxidative stress products (ROS, NO), MHC-II expression, and inflammatory cytokines in response to LPS and VILI in CD11bloLy6Chi monocytes was ameliorated by parecoxib.ConclusionParecoxib-induced alleviation of oxidative stress and inflammation in lung-recruited Ly6Chi monocytes may partly explain the beneficial action of COX-2 inhibition in VILI.Copyright © 2020 by the Shock Society.

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