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Regulation of Endothelial Cell Barrier Disruption in Acute Lung Injury by Autophagy
Author(s) -
Spencer Spencer,
Leonard Antony,
Grose Valerie,
Fazal Fabeha,
Rahman Arshad
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1074.4
Subject(s) - autophagy , proinflammatory cytokine , adherens junction , lung , endothelial stem cell , microbiology and biotechnology , vascular permeability , lipopolysaccharide , pulmonary edema , medicine , inflammation , chemistry , pharmacology , cancer research , immunology , biology , cell , pathology , apoptosis , cadherin , in vitro , biochemistry
Recent studies have implicated autophagy in many disorders including pulmonary diseases. However, the role of autophagy in endothelial cell (EC) barrier dysfunction and its relevance in the context of acute lung injury (ALI) remains uncertain. Here, we provide evidence that autophagy is a critical component of EC barrier disruption in ALI. Using an aerosolized bacterial lipopolysaccharide (LPS) inhalation mouse model of ALI, we found that administration of autophagy inhibitor 3‐methyladenine (3‐MA), either prophylactically or therapeutically, markedly reduced lung vascular leakage and tissue edema. Inhibiting autophagy by this approach also reduced the levels of proinflammatory mediators and lung neutrophil sequestration induced by LPS. To test the possibility that autophagy in EC could contribute to lung vascular injury, we addressed its role in the mechanism of EC barrier disruption. Pretreatment of cells with 3‐MA inhibited thrombin‐induced barrier disruption by inhibiting the cleavage and loss of VE‐cadherin at adherens junctions. 3‐MA was also effective in protecting against thrombin‐induced actin stress fiber formation. Together, these data reveal a novel role of autophagy in causing EC barrier dysfunction and lung microvascular permeability associated with ALI. Support or Funding Information This work was supported in part by National Heart, Lung, and Blood Institute Grants HL116632 and HL130870.