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Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation
Published on: June 30, 2014
Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function
George Su1, Maki Hodnett, Nanyan Wu
1Lung Biology Center, Division of Pulmonary and Critical Care Medicine, Laboratory of Surgical Research, Department of Anesthesia, and Cardiovascular Research Institute, University of California, San Francisco, California 94158, USA.
American Journal of Respiratory Cell and Molecular Biology
|November 3, 2006
Summary
Blocking integrin alphavbeta5 prevents lung vascular permeability in acute lung injury (ALI). This discovery highlights alphavbeta5 as a key regulator and potential therapeutic target for respiratory failure.
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Integrin Signaling
Background:
- Increased lung vascular permeability is a major factor in acute lung injury (ALI) and respiratory failure.
- Understanding the molecular mechanisms regulating pulmonary vascular permeability is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of integrin alphavbeta5 in the development of lung vascular permeability in ALI.
- To determine if targeting alphavbeta5 could serve as a therapeutic strategy for ALI.
Main Methods:
- Utilized function-blocking antibodies against integrin alphavbeta5 in rat and mouse models of ALI (ischemia-reperfusion and ventilation-induced lung injury).
- Employed knockout mice lacking the integrin beta5 subunit.
- Assessed pulmonary endothelial cell monolayer permeability and actin stress fiber formation in response to vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta), and thrombin.
Main Results:
- A function-blocking antibody against alphavbeta5 significantly prevented lung vascular permeability in both ALI models.
- Beta5 integrin knockout mice were protected from lung vascular permeability during ventilation-induced lung injury.
- Blocking or genetic absence of alphavbeta5 inhibited permeability increases and actin stress fiber formation in pulmonary endothelial cells induced by VEGF, TGF-beta, and thrombin.
Conclusions:
- Integrin alphavbeta5 is a central regulator of increased pulmonary vascular permeability in ALI.
- Alphavbeta5 mediates pulmonary endothelial cell permeability by influencing interactions with the actin cytoskeleton.
- Targeting integrin alphavbeta5 represents a promising therapeutic approach for managing ALI.
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