TGF-beta is a critical mediator of acute lung injury

J Clin Invest. 2001 Jun;107(12):1537-44. doi: 10.1172/JCI11963.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm*
  • Bleomycin
  • Blood-Air Barrier / physiology
  • Cells, Cultured
  • Endotoxins
  • Glutathione / metabolism
  • Integrins / genetics
  • Mice
  • Mice, Knockout
  • Protein Serine-Threonine Kinases
  • Pulmonary Alveoli / metabolism
  • Pulmonary Edema / etiology
  • Pulmonary Edema / pathology
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / administration & dosage
  • Respiratory Distress Syndrome / etiology*
  • Respiratory Distress Syndrome / metabolism
  • Respiratory Distress Syndrome / pathology
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / physiology*


  • Antigens, Neoplasm
  • Endotoxins
  • Integrins
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • integrin alphavbeta6
  • Bleomycin
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II
  • Glutathione