Zhang, C and Hu, S and Zosky, GR and Wei, X and Shu, S and Wang, D and Chai, X, Paracoxib alleviates ventilator-induced lung injury through functional modulation of lung-recruited CD11bloLy6Chi monocytes, Shock, 55, (2) pp. 236-243. ISSN 1073-2322 (2020) [Refereed Article]
Copyright 2020 Shock Society
Methods: Mice 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 hour 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 Ly6C 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.
Results: Exposure 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 CD11bLy6C 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 CD11bLy6C monocytes was ameliorated by parecoxib.
Conclusion: Parecoxib-induced alleviation of oxidative stress and inflammation in lung-recruited Ly6C monocytes may partly explain the beneficial action of COX-2 inhibition in VILI.
|Item Type:||Refereed Article|
|Keywords:||paracoxib, mechanical ventilation, macrophages, COX-2, parecoxib, lung-recruited Ly6C(hi) monocytes, two-hit, ventilator-induced lung injury|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Respiratory diseases|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Zosky, GR (Professor Graeme Zosky)|
|Deposited By:||Menzies Institute for Medical Research|
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