Am. J. Respir. Cell Mol. Biol.,
Volume 21, Number 2, August, 1999 275-282
Decreased Intracellular Iron Availability Suppresses Epithelial Cell
Surface Plasmin Generation
Transcriptional and Post-transcriptional Effects on u-PA and PAI-1 Expression
Takashi
Hasegawa,
Lise
Sorensen,
Hidemi
Ooi,
and
Bruce C.
Marshall
Division of Respiratory, Critical Care and Occupational Medicine, Department of Internal Medicine, Salt Lake
VA Medical Center and the University of Utah Health Sciences Center, Salt Lake City, Utah
Iron and iron metabolism are critical in a variety of physiologic and pathophysiologic processes, including
lung injury and repair. The plasmin/plasminogen activator (PA) system is involved in the extensive remodeling process that follows acute lung injury, and alveolar epithelial cells play a key role in this repair process. Herein we report that decreased intracellular iron availability markedly suppresses cell-surface plasmin generation by A549 human carcinoma-derived pulmonary epithelial cells. This effect is mediated by
concomitant downregulation of urokinase-type PA and upregulation of PA inhibitor-type 1 expression.
Northern analyses, runoff transcription assays, and messenger RNA half-life experiments using actinomycin demonstrate that transcriptional and post-transcriptional mechanisms are operative. Given these potent
in vitro effects on the plasmin/PA system, we speculate that adequate intracellular iron stores are important
for successful repair of acute lung injury.
