title: TGF-beta is a critical mediator of acute lung injury.
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.
authors: Departments of Anesthesia and Surgery, University of California San Francisco, San Francisco, California 94110, USA.
authors: J F
authors: JF
authors: Pittet
authors: M J
authors: MJ
authors: Griffiths
authors: T
authors: T
authors: Geiser
authors: N
authors: N
authors: Kaminski
authors: S L
authors: SL
authors: Dalton
authors: X
authors: X
authors: Huang
authors: L A
authors: LA
authors: Brown
authors: P J
authors: PJ
authors: Gotwals
authors: V E
authors: VE
authors: Koteliansky
authors: M A
authors: MA
authors: Matthay
authors: D
authors: D
authors: Sheppard
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm; D001761:Bleomycin; D015824:Blood-Air Barrier / Q000502:physiology; D002478:Cells, Cultured; D004731:Endotoxins; D005978:Glutathione / Q000378:metabolism; D016023:Integrins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases; D011650:Pulmonary Alveoli / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000008:administration & dosage; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D004731:Endotoxins; D016023:Integrins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C073878:integrin alphavbeta6; D001761:Bleomycin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D005978:Glutathione