Integrin alphavbeta5 regulates lung vascular permeability and pulmonary endothelial barrier function

Department of Surgery, University of California, San Francisco, San Francisco, California, United States
American Journal of Respiratory Cell and Molecular Biology (Impact Factor: 3.99). 04/2007; 36(3):377-86. DOI: 10.1165/rcmb.2006-0238OC
Source: PubMed


Increased lung vascular permeability is an important contributor to respiratory failure in acute lung injury (ALI). We found that a function-blocking antibody against the integrin alphavbeta5 prevented development of lung vascular permeability in two different models of ALI: ischemia-reperfusion in rats (mediated by vascular endothelial growth factor [VEGF]) and ventilation-induced lung injury (VILI) in mice (mediated, at least in part, by transforming growth factor-beta [TGF-beta]). Knockout mice homozygous for a null mutation of the integrin beta5 subunit were also protected from lung vascular permeability in VILI. In pulmonary endothelial cells, both the genetic absence and blocking of alphavbeta5 prevented increases in monolayer permeability induced by VEGF, TGF-beta, and thrombin. Furthermore, actin stress fiber formation induced by each of these agonists was attenuated by blocking alphavbeta5, suggesting that alphavbeta5 regulates induced pulmonary endothelial permeability by facilitating interactions with the actin cytoskeleton. These results identify integrin alphavbeta5 as a central regulator of increased pulmonary vascular permeability and a potentially attractive therapeutic target in ALI.

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Available from: Dean Sheppard, May 22, 2015
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    • "In addition, microscopy analysis explored that hypoxia alone induces slight alveolar epithelium and capillary endothelium disruption and swelling, while combined hypoxia and exercise significantly increased endothelium swelling and disruption. In the study, the alveolar-capillary permeability is measured to the integrity of alveolar-capillary barrier by Evan’s blue method [24,27]. Moreover, in our study, HR mice, present the medium situation symptoms that from normal to HAPE development, which could correspond to subclinical HAPE in human. "
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    • "Focal adhesions, sites of close contact between cell-cell and cell-extracellular matrix, are essential for normal cell growth, differentiation, inter-and intracellular communication, and tissue integrity (Mehta and Malik, 2006; Mehta et al., 2002). Among the protein complexes associated with focal adhesions, focal adhesion kinase (FAK) and paxillin play an important role in the transmission of integrininduced cytoplasmic signals and in the reorganization of actin cytoskeleton (Katsumi et al., 2004; Parsons, 2003; Su et al., 2007). FAK, an ~125-kDa tyrosine kinase, is activated primarily through integrin-mediated cell adhesion to extracellular matrix and to a lesser extent by growth factors, bioactive lipids, neuropeptides, and ROS (Mehta and Malik, 2006). "
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    • "αvβ5 and/or αvβ6) other than αvβ5 is likely to be responsible for the protective effects of RGDS on BAL protein accumulation. Indeed, a blocking antibody against the integrin αvβ5 or αvβ6 protected development of lung vascular permeability in different models of acute lung injury [35-37]. Additional studies are required to identify a physiological role of β3 integrin in the development of pulmonary edema during acute lung injury. "
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