VEGF Production by Ly6C+high Monocytes Contributes to Ventilator-Induced Lung Injury

Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilator-induced lung injury (VILI). Ly6C+high monocytes are involved in the pathogenesis of VILI. In this study, we investig...

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Bibliographic Details
Published in:PloS one 2016-10, Vol.11 (10), p.e0165317-e0165317
Main Authors: Shi, Chung-Sheng, Huang, Tzu-Hsiung, Lin, Chin-Kuo, Li, Jhy-Ming, Chen, Mei-Hsin, Tsai, Mei-Ling, Chang, Chih-Ching
Format: Article
Language:English
Subjects:
Alveoli
Anesthesia
Angiogenesis
Animals
Antigens, Ly - metabolism
Apoptosis
Biology and Life Sciences
Bisphosphonates
Blood Gas Analysis
Bronchoalveolar lavage
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - cytology
Bronchus
Cell Membrane Permeability - drug effects
Cell permeability
Clinical medicine
Clodronic acid
Critical care
Cytokines
Cytometry
Disease Models, Animal
Drug dosages
Endothelial cells
Endothelial Cells - cytology
Endothelial Cells - metabolism
Flow cytometry
Hospitals
Infiltration
Inflammation
Injuries
Interleukin 6
Interleukin-6 - metabolism
Intravenous administration
Laboratory animals
Leukocytes
Leukocytes (mononuclear)
Lipopolysaccharides
Lipopolysaccharides - toxicity
Liposomes
Lung - pathology
Lungs
Male
Mechanical ventilation
Medicine
Medicine and Health Sciences
Membrane permeability
Mice
Mice, Inbred C57BL
Monocytes
Monocytes - cytology
Monocytes - drug effects
Monocytes - metabolism
Neutrophils
Neutrophils - cytology
Neutrophils - drug effects
Neutrophils - metabolism
Nitric oxide
Oxidative stress
Pathogenesis
Permeability
Physical Sciences
Physiology
Pneumoviridae
Proteins
Regression Analysis
Respiration, Artificial - adverse effects
Respiratory failure
Rodents
Severity of Illness Index
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
Ventilation
Ventilator-Induced Lung Injury - metabolism
Ventilator-Induced Lung Injury - pathology
Ventilators
White blood cells
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Summary:Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilator-induced lung injury (VILI). Ly6C+high monocytes are involved in the pathogenesis of VILI. In this study, we investigated whether pulmonary infiltrated Ly6C+high monocytes produce vascular endothelial growth factor (VEGF) and contribute to VILI. A clinically relevant two-hit mouse model of VILI, with intravenous lipopolysaccharide (LPS, 20 ng/mouse) immediately before high tidal volume (HTV, 20 mL/kg) ventilation (LPS+HTV), was established. Blood gas and respiratory mechanics were measured to ensure the development of VILI. Flow cytometry and histopathological analyses revealed pulmonary infiltration of leukocytes subsets. Clodronate liposomes were intravenously injected to deplete pulmonary monocytes. In vitro endothelial cell permeability assay with sorted Ly6C+high monocytes condition media assessed the role of Ly6C+high monocytes in vascular permeability. LPS+HTV significantly increased total proteins, TNF-α, IL-6, vascular endothelial growth factor (VEGF) and mononuclear cells in the bronchoalveolar lavage fluid (BALF). Pulmonary Ly6C+high monocytes (SSClowCD11b+F4/80+Ly6C+high), but not Ly6C+low monocytes (SSClowCD11b+F4/80+Ly6C+low), were significantly elevated starting at 4 hr. Clodronate liposomes were able to significantly reduce pulmonary Ly6C+high monocytes, and VEGF and total protein in BALF, and restore PaO2/FiO2. There was a strong correlation between pulmonary Ly6C+high monocytes and BALF VEGF (R2 = 0.8791, p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0165317