Back to Search Start Over

Cyclooxygenase-2 Activity Regulates Recruitment of VEGF-Secreting Ly6Chigh Monocytes in Ventilator-Induced Lung Injury

Authors :
Tzu-Hsiung Huang
Pin-Hui Fang
Jhy-Ming Li
Huan-Yuan Ling
Chieh-Mo Lin
Chung-Sheng Shi
Source :
International Journal of Molecular Sciences, Vol 20, Iss 7, p 1771 (2019)
Publication Year :
2019
Publisher :
MDPI AG, 2019.

Abstract

Mechanical ventilation is usually required for saving lives in critically ill patients; however, it can cause ventilator-induced lung injury (VILI). As VEGF-secreting Ly6Chigh monocytes are involved in VILI pathogenesis, we investigated whether cyclooxygenase-2 (COX-2) activity regulates the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI. The clinically relevant two-hit mouse model of VILI, which involves the intravenous injection of lipopolysaccharide prior to high tidal volume (HTV)-mechanical ventilation, was used in this study. To investigate the role of COX-2 in the recruitment of VEGF-secreting Ly6Chigh monocytes during VILI, celecoxib, which is a clinical COX-2 inhibitor, was administered 1 h prior to HTV-mechanical ventilation. Pulmonary vascular permeability and leakage, inflammatory leukocyte infiltration, and lung oxygenation levels were measured to assess the severity of VILI. HTV-mechanical ventilation significantly increased the recruitment of COX-2-expressing Ly6Chigh, but not Ly6Clow, monocytes. Celecoxib significantly diminished the recruitment of Ly6Chigh monocytes, attenuated the levels of VEGF and total protein in bronchoalveolar lavage fluid, and restored pulmonary oxygenation during VILI. Our findings demonstrate that COX-2 activity is important in the recruitment of VEGF-secreting Ly6Chigh monocytes, which are involved in VILI pathogenesis, and indicate that the suppression of COX-2 activity might be a useful strategy in mitigating VILI.

Details

Language :
English
ISSN :
14220067
Volume :
20
Issue :
7
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.3845ffb97f5d4de8a27982e6d2251094
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms20071771