Differential Response of Human Lung Epithelial Cells to Fas-Induced Apoptosis
- 1 June 2004
- journal article
- Published by Elsevier BV in The American Journal of Pathology
- Vol. 164 (6), 1949-1958
- https://doi.org/10.1016/s0002-9440(10)63755-8
Abstract
The Fas (CD95)/Fas ligand (CD178) system plays an important role in epithelial damage during the acute respiratory distress syndrome. The goal of this study was to determine whether proximal and distal human lung epithelial cells differ in their sensitivity to Fas ligand (rh-sFasL), and whether the response of lung epithelium to Fas ligation is modulated by proinflammatory cytokines. Although the expression of both Fas message and protein was similar in proximal and distal lung epithelial cells, only distal cells became apoptotic when exposed to serial dilutions of rh-sFasL. Stimulation with tumor necrosis factor-α, interleukin-1β, or interferon-γ significantly increased the sensitivity of proximal cells to rh-sFasL, and exposure to either tumor necrosis factor-α or interferon-γ enhanced the sensitivity of distal cells to Fas ligation. These findings suggest that in normal human lungs, the responses of the epithelium to Fas ligation become more pronounced from proximal to distal locations. Furthermore, proinflammatory cytokines sensitize lung epithelium to Fas-induced death. These findings are relevant for understanding the role of the Fas/FasL system in acute lung injury, in which epithelial damage occurs primarily in distal airway and alveolar epithelium, whereas sFasL is present throughout the airspaces.Keywords
This publication has 40 references indexed in Scilit:
- Fas (CD95) Induces Alveolar Epithelial Cell Apoptosis in VivoThe American Journal of Pathology, 2001
- Interferon-? sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosisJournal of Cellular Physiology, 2000
- Susceptibility to FAS-induced apoptosis in human nontumoral enterocytes: Role of costimulatory factorsJournal of Cellular Physiology, 1999
- Fas Antigen (CD95) in pure erythroid cell line AS-E2 is induced by interferon-γ and tumor necrosis factor-α and potentiates apoptotic deathExperimental Hematology, 1999
- Fas ligand is not only expressed in immune privileged human organs but is also coexpressed with Fas in various epithelial tissues.Molecular Pathology, 1997
- Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover.The Journal of cell biology, 1996
- The CD95 (APO-1/Fas) Receptor Activates NF- B Independently of Its Cytotoxic FunctionPublished by Elsevier BV ,1996
- Purification and characterization of the Fas-ligand that induces apoptosis.The Journal of Experimental Medicine, 1994
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993
- The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosisCell, 1991