Published ahead of print on September 21, 2006, doi:10.1165/rcmb.2006-0133OC Am. J. Respir. Cell Mol. Biol., Volume 36, Number 3, March 2007, 270-275 A more recent version of this article appeared on March 1, 2007
Submitted on April 4, 2006 Epithelial Cell Apoptosis by FasL-positive Myofibroblasts in Lung FibrosisRegina Golan-Gerstl1,1 Lung Cellular and Molecular Biology Laboratory, Hadassah-Hebrew University Medical Center, Institute of Pulmonary Medicine, Jerusalem, Israel, 2 Lung Cellular and Molecular Biology Laboratory, Hadassah-Hebrew University Medical Center, Institute of Pulmonary Medicine, Jerusalem, Israel; Department of Pathology, Boston University School of Medicine, Boston, MA, USA * To whom correspondence should be addressed. E-mail: raffi{at}hadassah.org.il.
The Fas/FasL apoptotic pathway has been shown to be involved in bleomycin-induced lung fibrosis. We examined the hypothesis that myofibroblasts from fibrotic lungs possess a cytotoxic phenotype that causes apoptosis of epithelial cells via the Fas/FasL pathway. We show in vivo epithelial cell apoptosis and associated upregulation of Fas and Fas apoptotic pathway genes in epithelial cells of lungs with bleomycin-induced fibrosis. In addition, we show that FasL surface molecules are overexpressed on
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SMA positive cells in mice with bleomycin-induced fibrosis, and in humans with idiopathic pulmonary fibrosis (IPF), which enables them to kill Fas-positive epithelial cells. In contrast, FasL-deficient myofibroblasts lose this myofibroblast cytotoxic phenotype, both in vivo and in vitro. In vivo, there was no bleomycin-induced epithelial cell apoptosis, as assessed by specific M30 staining in chimeric FasL-deficient mice that lacked FasL positive myofibroblasts. In vitro, FasL positive-, but not FasL-negative myofibroblasts, induce MLE cell apoptosis. Thus myofibroblast cytotoxicity may underlie the absence of re-epithelialization, resulting in persistent lung
fibrosis.
