TGF-beta is a critical mediator of acute lung injury

We have shown that the integrin alphav betaG activates latent TGF-beta in t he lungs and skin. We show here that mice lacking this integrin are complet ely protected from pulmonary edema in a model of bleomycin-induced acute lu ng injury (ALI). Pharmacologic inhibition of TGF-beta also protected wild-t ype mice from pulmonary edema induced by bleomycin or Escherichia coli endo toxin. TGF-beta directly increased alveolar epithelial permeability in vitr o by a mechanism that involved depletion of intracellular glutathione. Thes e data suggest that integrin-mediated local activation of TGF-beta is criti cal to the development of pulmonary edema in ALI and that blocking TGF-beta or its activation could be effective treatments for this currently untreat able disorder.