TGF-β is a critical mediator of acute lung injury |
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| Authors: | Jean-Francois Pittet Mark J.D. Griffiths Tom Geiser Naftali Kaminski Stephen L. Dalton Xiaozhu Huang Lou Anne S. Brown Phillip J. Gotwals Victor E. Koteliansky Michael A. Matthay Dean Sheppard |
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| Affiliation: | Departments of Anesthesia and Surgery, University of California San Francisco, San Francisco, California 94110, USA. |
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| Abstract: | We have shown that the integrin alphavbeta6 activates latent TGF-beta in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-beta also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-beta directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-beta is critical to the development of pulmonary edema in ALI and that blocking TGF-beta or its activation could be effective treatments for this currently untreatable disorder. |
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