HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by De Paepe, M. E. Articles by Sharma, S. Search for Related Content PubMed PubMed Citation Articles by De Paepe, M. E. Articles by Sharma, S.

Hyperoxia-induced apoptosis and Fas/FasL expression in lung epithelial cells

Departments of ¹Pathology and ²Pediatrics, Women and Infants Hospital and Brown Medical School, Providence, Rhode Island

Submitted 29 November 2004 ; accepted in final form 8 June 2005

Alveolar epithelial apoptosis is an important feature of hyperoxia-induced lung injury in vivo and has been described in the early stages of bronchopulmonary dysplasia (chronic lung disease of preterm newborn). Molecular regulation of hyperoxia-induced alveolar epithelial cell death remains incompletely understood. In view of functional involvement of Fas/FasL system in physiological postcanalicular type II cell apoptosis, we speculated this system may also be a critical regulator of hyperoxia-induced apoptosis. The aim of this study was to investigate the effects of hyperoxia on apoptosis and apoptotic gene expression in alveolar epithelial cells. Apoptosis was studied by TUNEL, electron microscopy, DNA size analysis, and caspase assays. Fas/FasL expression was determined by Western blot analysis and RPA. We determined that in MLE-12 cells exposed to hyperoxia, caspase-mediated apoptosis was the first morphologically and biochemically recognizable mode of cell death, followed by necrosis of residual adherent cells. The apoptotic stage was associated with a threefold upregulation of Fas mRNA and protein expression and increased susceptibility to direct Fas receptor activation, concomitant with a threefold increase of FasL protein levels. Fas gene silencing by siRNAs significantly reduced hyperoxia-induced apoptosis. In murine fetal type II cells, hyperoxia similarly induced markedly increased Fas/FasL protein expression, confirming validity of results obtained in transformed MLE-12 cells. Our findings implicate the Fas/FasL system as an important regulator of hyperoxia-induced type II cell apoptosis. Elucidation of regulation of hyperoxia-induced lung apoptosis may lead to alternative therapeutic strategies for perinatal or adult pulmonary diseases characterized by dysregulated type II cell apoptosis.

programmed cell death; bronchopulmonary dysplasia; chronic lung disease; oxygen; alveolar epithelial type II cell

This article has been cited by other articles:

				R. L. Zemans, S. P. Colgan, and G. P. Downey Transepithelial Migration of Neutrophils: Mechanisms and Implications for Acute Lung Injury Am. J. Respir. Cell Mol. Biol., May 1, 2009; 40(5): 519 - 535. [Abstract] [Full Text] [PDF]

				Q. Mao, S. Gundavarapu, C. Patel, A. Tsai, F. I. Luks, and M. E. De Paepe The Fas System Confers Protection against Alveolar Disruption in Hyperoxia-Exposed Newborn Mice Am. J. Respir. Cell Mol. Biol., December 1, 2008; 39(6): 717 - 729. [Abstract] [Full Text] [PDF]

				P. S. Tang, M. Mura, R. Seth, and M. Liu Acute lung injury and cell death: how many ways can cells die? Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L632 - L641. [Abstract] [Full Text] [PDF]

				M. Perl, C.-S. Chung, U. Perl, J. Lomas-Neira, M. de Paepe, W. G. Cioffi, and A. Ayala Fas-induced Pulmonary Apoptosis and Inflammation during Indirect Acute Lung Injury Am. J. Respir. Crit. Care Med., September 15, 2007; 176(6): 591 - 601. [Abstract] [Full Text] [PDF]

				Z. G. Fridlender, P. Y. Cohen, O. Golan, N. Arish, S. Wallach-Dayan, and R. Breuer Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis Eur. Respir. J., August 1, 2007; 30(2): 205 - 213. [Abstract] [Full Text] [PDF]

				R. Choo-Wing, J. H. Nedrelow, R. J. Homer, J. A. Elias, and V. Bhandari Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L142 - L150. [Abstract] [Full Text] [PDF]

				M. A. Alejandre-Alcazar, G. Kwapiszewska, I. Reiss, O. V. Amarie, L. M. Marsh, J. Sevilla-Perez, M. Wygrecka, B. Eul, S. Kobrich, M. Hesse, et al. Hyperoxia modulates TGF-beta/BMP signaling in a mouse model of bronchopulmonary dysplasia Am J Physiol Lung Cell Mol Physiol, February 1, 2007; 292(2): L537 - L549. [Abstract] [Full Text] [PDF]

				D. Xu, J. R. Guthrie, S. Mabry, T. M. Sack, and W. E. Truog Mitochondrial aldehyde dehydrogenase attenuates hyperoxia-induced cell death through activation of ERK/MAPK and PI3K-Akt pathways in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L966 - L975. [Abstract] [Full Text] [PDF]

				M. Yee, P. F. Vitiello, J. M. Roper, R. J. Staversky, T. W. Wright, S. A. McGrath-Morrow, W. M. Maniscalco, J. N. Finkelstein, and M. A. O'Reilly Type II epithelial cells are critical target for hyperoxia-mediated impairment of postnatal lung development Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L1101 - L1111. [Abstract] [Full Text] [PDF]