Pittet J F, Griffiths M J, Geiser T, Kaminski N, Dalton S L, Huang X, Brown L A, Gotwals P J, Koteliansky V E, Matthay M A, Sheppard D
Departments of Anesthesia and Surgery, University of California San Francisco, San Francisco, California 94110, USA.
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.
我们已经证明，整合素αvβ6可激活肺和皮肤中的潜伏性转化生长因子β（TGF-β）。我们在此表明，在博来霉素诱导的急性肺损伤（ALI）模型中，缺乏这种整合素的小鼠可完全免受肺水肿的影响。对TGF-β的药理抑制也可保护野生型小鼠免受博来霉素或大肠杆菌内毒素诱导的肺水肿。TGF-β在体外通过一种涉及细胞内谷胱甘肽耗竭的机制直接增加肺泡上皮通透性。这些数据表明，整合素介导的TGF-β局部激活对于ALI中肺水肿的发展至关重要，并且阻断TGF-β或其激活可能是治疗这种目前无法治疗的疾病的有效方法。
