Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand

Karl L. Serrao, James D. Fortenberry, Marilyn L. Owens, Frank L. Harris, Lou Ann S Brown

Research output: Contribution to journalArticle

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Abstract

Neutrophils release soluble Fas ligand (sFasL), which can induce apoptosis in certain Fas-bearing cell types (Liles WC, Kiener PA, Ledbetter JA, Aruffo A, and Klebanoff SJ. J Exp Med 184: 429-440, 1996). We hypothesized that neutrophils could induce alveolar epithelial apoptosis via release of sFasL. A549 pulmonary adenocarcinoma cells expressed surface Fas and underwent cell death (10 ± 7% viability) and DNA fragmentation (354 ± 98% of control cells) when incubated with agonistic CD95/Fas monoclonal antibody (P < 0.05). Coincubation with human neutrophils induced significant A549 cell death at 48 (51 ± 9% viability; P < 0.05) and 72 h (25 ± 10%; P < 0.05) and increased DNA fragmentation (178 ± 42% of control cells; P < 0.05), with morphological characteristics of apoptosis. The addition of antioxidants did not inhibit apoptosis. sFasL concentrations were maximally increased in coculture medium at 24 h (4.9 ± 0.7 ng/ml; P < 0.05). Neutrophil-induced A549 cell apoptosis was blocked by inhibitory anti-Fas (42 ± 6% of control cells; P < 0.05) and anti-FasL monoclonal antibodies (29 ± 3%; P < 0.05). Human neutrophils and Fas similarly affected murine primary alveolar epithelial cell bilayers, and caspase activation occurred in response to Fas exposure. We conclude that neutrophils undergoing spontaneous apoptosis induce A549 cell death and DNA fragmentation, independent of the oxidative burst, that is mediated by sFasL.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number2 24-2
StatePublished - Feb 2001
Externally publishedYes

Fingerprint

Fas Ligand Protein
Neutrophils
Epithelial Cells
Apoptosis
Lung
DNA Fragmentation
Cell Death
Monoclonal Antibodies
Alveolar Epithelial Cells
Respiratory Burst
Caspases
Coculture Techniques
Antioxidants
A549 Cells

Keywords

  • Alveolar epithelium
  • Fas antigen

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Serrao, K. L., Fortenberry, J. D., Owens, M. L., Harris, F. L., & Brown, L. A. S. (2001). Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand. American Journal of Physiology - Lung Cellular and Molecular Physiology, 280(2 24-2).

Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand. / Serrao, Karl L.; Fortenberry, James D.; Owens, Marilyn L.; Harris, Frank L.; Brown, Lou Ann S.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 280, No. 2 24-2, 02.2001.

Research output: Contribution to journalArticle

Serrao, Karl L. ; Fortenberry, James D. ; Owens, Marilyn L. ; Harris, Frank L. ; Brown, Lou Ann S. / Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 ; Vol. 280, No. 2 24-2.
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abstract = "Neutrophils release soluble Fas ligand (sFasL), which can induce apoptosis in certain Fas-bearing cell types (Liles WC, Kiener PA, Ledbetter JA, Aruffo A, and Klebanoff SJ. J Exp Med 184: 429-440, 1996). We hypothesized that neutrophils could induce alveolar epithelial apoptosis via release of sFasL. A549 pulmonary adenocarcinoma cells expressed surface Fas and underwent cell death (10 ± 7{\%} viability) and DNA fragmentation (354 ± 98{\%} of control cells) when incubated with agonistic CD95/Fas monoclonal antibody (P < 0.05). Coincubation with human neutrophils induced significant A549 cell death at 48 (51 ± 9{\%} viability; P < 0.05) and 72 h (25 ± 10{\%}; P < 0.05) and increased DNA fragmentation (178 ± 42{\%} of control cells; P < 0.05), with morphological characteristics of apoptosis. The addition of antioxidants did not inhibit apoptosis. sFasL concentrations were maximally increased in coculture medium at 24 h (4.9 ± 0.7 ng/ml; P < 0.05). Neutrophil-induced A549 cell apoptosis was blocked by inhibitory anti-Fas (42 ± 6{\%} of control cells; P < 0.05) and anti-FasL monoclonal antibodies (29 ± 3{\%}; P < 0.05). Human neutrophils and Fas similarly affected murine primary alveolar epithelial cell bilayers, and caspase activation occurred in response to Fas exposure. We conclude that neutrophils undergoing spontaneous apoptosis induce A549 cell death and DNA fragmentation, independent of the oxidative burst, that is mediated by sFasL.",
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