Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury.

Naunyn-Schmiedeberg's Archives of Pharmacology
Kengo TomitaYuichi Hattori

Abstract

Vascular endothelial growth factor (VEGF) is a prime regulator of vascular permeability. Acute lung injury (ALI) is characterized by high-permeability pulmonary edema in addition to refractory hypoxemia and diffuse pulmonary infiltrates. In this study, we examined whether VEGF can be implicated as a pulmonary vascular permeability factor in sepsis-associated ALI. We found that a great increase in lung vascular leak occurred in mice instilled intranasally with lipopolysaccharide (LPS), as assessed by IgM levels in bronchoalveolar lavage fluid. Treatment with the VEGF-neutralizing monoclonal antibody bevacizumab significantly reduced this hyperpermeability response, suggesting active participation of VEGF in non-cardiogenic lung edema associated with LPS-induced ALI. However, this was not solely attributable to excessive levels of intrapulmonary VEGF. Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pu...Continue Reading

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Citations

Aug 18, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Tokiko SuzukiYuichi Hattori

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
bronchoalveolar
PCR
Protein Assay
electrophoresis

Software Mentioned

Prism
GraphPad

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