We have shown that the integrin αvβ6 activates latent TGF-β 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-β also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-β 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-β is critical to the development of pulmonary edema in ALI and that blocking TGF-β or its activation could be effective treatments for this currently untreatable disorder.
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
Usage data is cumulative from April 2023 through April 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 917 | 237 |
93 | 47 | |
Figure | 138 | 12 |
Citation downloads | 20 | 0 |
Totals | 1,168 | 296 |
Total Views | 1,464 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.