VEGF production by Ly6C+high monocytes contributes to ventilator-induced lung injury

Chung Sheng Shi, Tzu Hsiung Huang, Chin Kuo Lin, Jhy Ming Li, Mei Hsin Chen, Mei-Ling Tsai, Chih-Ching Chang

Research output: Contribution to journalArticle

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Abstract

Background Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilatorinduced 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. Methods 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. Results 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 (SSClow CD11b CD11b+F4/80 + Ly6C Ly6Chgih+), but not Ly6C+low monocytes (SSClow CD11b+ F4/80+ Ly6Cwol+), 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<0.001). Moreover, sorted Ly6C+high monocytes were able to produce VEGF, resulting in an increased permeability of endothelial cell monolayer in an in vitro endothelial cell permeability assay. Conclusion VEGF produced by pulmonary infiltrated Ly6C+high monocytes regulates vasculature permeability in a two-hit model of HTV-induced lung injury. Ly6C+high monocytes play an important role in the pathogenesis of VILI.

Original languageEnglish
Article numbere0165317
JournalPloS one
Volume11
Issue number10
DOIs
Publication statusPublished - 2016 Oct 1

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Ventilator-Induced Lung Injury
ventilators
vascular endothelial growth factors
production economics
monocytes
Vascular Endothelial Growth Factor A
Monocytes
lungs
Lung Injury
Endothelial cells
Clodronic Acid
Lung
Liposomes
Fluids
Permeability
Assays
permeability
Bronchoalveolar Lavage Fluid
Respiratory mechanics
Endothelial Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Shi, Chung Sheng ; Huang, Tzu Hsiung ; Lin, Chin Kuo ; Li, Jhy Ming ; Chen, Mei Hsin ; Tsai, Mei-Ling ; Chang, Chih-Ching. / VEGF production by Ly6C+high monocytes contributes to ventilator-induced lung injury. In: PloS one. 2016 ; Vol. 11, No. 10.
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abstract = "Background Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilatorinduced 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. Methods 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. Results 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 (SSClow CD11b CD11b+F4/80 + Ly6C Ly6Chgih+), but not Ly6C+low monocytes (SSClow CD11b+ F4/80+ Ly6Cwol+), 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<0.001). Moreover, sorted Ly6C+high monocytes were able to produce VEGF, resulting in an increased permeability of endothelial cell monolayer in an in vitro endothelial cell permeability assay. Conclusion VEGF produced by pulmonary infiltrated Ly6C+high monocytes regulates vasculature permeability in a two-hit model of HTV-induced lung injury. Ly6C+high monocytes play an important role in the pathogenesis of VILI.",
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VEGF production by Ly6C+high monocytes contributes to ventilator-induced lung injury. / Shi, Chung Sheng; Huang, Tzu Hsiung; Lin, Chin Kuo; Li, Jhy Ming; Chen, Mei Hsin; Tsai, Mei-Ling; Chang, Chih-Ching.

In: PloS one, Vol. 11, No. 10, e0165317, 01.10.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - VEGF production by Ly6C+high monocytes contributes to ventilator-induced lung injury

AU - Shi, Chung Sheng

AU - Huang, Tzu Hsiung

AU - Lin, Chin Kuo

AU - Li, Jhy Ming

AU - Chen, Mei Hsin

AU - Tsai, Mei-Ling

AU - Chang, Chih-Ching

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Background Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilatorinduced 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. Methods 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. Results 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 (SSClow CD11b CD11b+F4/80 + Ly6C Ly6Chgih+), but not Ly6C+low monocytes (SSClow CD11b+ F4/80+ Ly6Cwol+), 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<0.001). Moreover, sorted Ly6C+high monocytes were able to produce VEGF, resulting in an increased permeability of endothelial cell monolayer in an in vitro endothelial cell permeability assay. Conclusion VEGF produced by pulmonary infiltrated Ly6C+high monocytes regulates vasculature permeability in a two-hit model of HTV-induced lung injury. Ly6C+high monocytes play an important role in the pathogenesis of VILI.

AB - Background Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilatorinduced 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. Methods 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. Results 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 (SSClow CD11b CD11b+F4/80 + Ly6C Ly6Chgih+), but not Ly6C+low monocytes (SSClow CD11b+ F4/80+ Ly6Cwol+), 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<0.001). Moreover, sorted Ly6C+high monocytes were able to produce VEGF, resulting in an increased permeability of endothelial cell monolayer in an in vitro endothelial cell permeability assay. Conclusion VEGF produced by pulmonary infiltrated Ly6C+high monocytes regulates vasculature permeability in a two-hit model of HTV-induced lung injury. Ly6C+high monocytes play an important role in the pathogenesis of VILI.

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