Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death

Vineet Bhandari, Rayman Choo-Wing, Chun G. Lee, Zhou Zhu, Jonathan H. Nedrelow, Geoffrey L. Chupp, Xucher Zhang, Michael A. Matthay, Lorraine B. Ware, Robert J. Homer, Patty J. Lee, Anke Geick, Antonin R. De Fougerolles, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

The angiogenic growth factor angiopoietin 2 (Ang2) destabilizes blood vessels, enhances vascular leak and induces vascular regression and endothelial cell apoptosis. We considered that Ang2 might be important in hyperoxic acute lung injury (ALI). Here we have characterized the responses in lungs induced by hyperoxia in wild-type and Ang2-/- mice or those given either recombinant Ang2 or short interfering RNA (siRNA) targeted to Ang2. During hyperoxia Ang2 expression is induced in lung epithelial cells, while hyperoxia-induced oxidant injury, cell death, inflammation, permeability alterations and mortality are ameliorated in Ang2-/- and siRNA-treated mice. Hyperoxia induces and activates the extrinsic and mitochondrial cell death pathways and activates initiator and effector caspases through Ang2-dependent pathways in vivo. Ang2 increases inflammation and cell death during hyperoxia in vivo and stimulates epithelial necrosis in hyperoxia in vitro. Ang2 in plasma and alveolar edema fluid is increased in adults with ALI and pulmonary edema. Tracheal Ang2 is also increased in neonates that develop bronchopulmonary dysplasia. Ang2 is thus a mediator of epithelial necrosis with an important role in hyperoxic ALI and pulmonary edema.

Original languageEnglish (US)
Pages (from-to)1286-1293
Number of pages8
JournalNature Medicine
Volume12
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

Fingerprint

Angiopoietin-2
Hyperoxia
Acute Lung Injury
Cell death
Cell Death
Pulmonary Edema
Small Interfering RNA
Blood Vessels
Necrosis
Initiator Caspases
Effector Caspases
Inflammation
Bronchopulmonary Dysplasia
Lung
Angiogenesis Inducing Agents
Endothelial cells
Blood vessels
Oxidants

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bhandari, V., Choo-Wing, R., Lee, C. G., Zhu, Z., Nedrelow, J. H., Chupp, G. L., ... Elias, J. A. (2006). Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nature Medicine, 12(11), 1286-1293. https://doi.org/10.1038/nm1494

Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. / Bhandari, Vineet; Choo-Wing, Rayman; Lee, Chun G.; Zhu, Zhou; Nedrelow, Jonathan H.; Chupp, Geoffrey L.; Zhang, Xucher; Matthay, Michael A.; Ware, Lorraine B.; Homer, Robert J.; Lee, Patty J.; Geick, Anke; De Fougerolles, Antonin R.; Elias, Jack A.

In: Nature Medicine, Vol. 12, No. 11, 11.2006, p. 1286-1293.

Research output: Contribution to journalArticle

Bhandari, V, Choo-Wing, R, Lee, CG, Zhu, Z, Nedrelow, JH, Chupp, GL, Zhang, X, Matthay, MA, Ware, LB, Homer, RJ, Lee, PJ, Geick, A, De Fougerolles, AR & Elias, JA 2006, 'Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death', Nature Medicine, vol. 12, no. 11, pp. 1286-1293. https://doi.org/10.1038/nm1494
Bhandari V, Choo-Wing R, Lee CG, Zhu Z, Nedrelow JH, Chupp GL et al. Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nature Medicine. 2006 Nov;12(11):1286-1293. https://doi.org/10.1038/nm1494
Bhandari, Vineet ; Choo-Wing, Rayman ; Lee, Chun G. ; Zhu, Zhou ; Nedrelow, Jonathan H. ; Chupp, Geoffrey L. ; Zhang, Xucher ; Matthay, Michael A. ; Ware, Lorraine B. ; Homer, Robert J. ; Lee, Patty J. ; Geick, Anke ; De Fougerolles, Antonin R. ; Elias, Jack A. / Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. In: Nature Medicine. 2006 ; Vol. 12, No. 11. pp. 1286-1293.
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