TGF-β is a critical mediator of acute lung injury

被引：388

作者：

Pittet, JF

Griffiths, MJD

Geiser, T

Kaminski, N

Dalton, SL

Huang, XZ

Brown, LAS

Gotwals, PJ

Koteliansky, VE

Matthay, MA

Sheppard, D

机构：

[1] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94110 USA

[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94110 USA

[3] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94110 USA

[4] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94110 USA

[5] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94110 USA

[6] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA

[7] USA Biogen Inc, Cambridge, MA USA

[8] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[9] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2001年 / 107卷 / 12期

关键词：

D O I：

10.1172/JCI11963

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

We have shown that the integrin alphav betaG 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.

引用

页码：1537 / 1544

页数：8

共 29 条

[1] AN ASSAY FOR TRANSFORMING GROWTH-FACTOR-BETA USING CELLS TRANSFECTED WITH A PLASMINOGEN-ACTIVATOR INHIBITOR-1 PROMOTER LUCIFERASE CONSTRUCT [J].