DOI: 10.1084/jem.192.5.647. FAS Ligand, Bcl-2, Granulocyte Colony-Stimulating Factor, and p38 Mitogen-Activated Protein Kinase

FAS Ligand, Bcl-2, Granulocyte Colony-Stimulating Factor, and p38 Mitogen-Activated Protein Kinase

10.1084/jem.192.5.647

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

The short life span of granulocytes, which limits many inflammatory responses, is thought to be influenced by the Bcl-2 protein family, death receptors such as CD95 (Fas/APO-1), stress-activated protein kinases such as p38 mitogen-activated protein kinase (MAPK), and proinflammatory cytokines like granulocyte colony-stimulating factor (G-CSF). To clarify the roles of these various regulators in granulocyte survival, we have investigated the spontaneous apoptosis of granulocytes in culture and that induced by Fas ligand or chemotherapeutic drugs, using cells from normal, CD95-deficient lpr, or vav-bcl-2 transgenic mice. CD95-induced apoptosis, which required receptor aggregation by recombinant Fas ligand or the membrane-bound ligand, was unaffected by G-CSF treatment or Bcl-2 overexpression. Conversely, spontaneous and drug-induced apoptosis occurred normally in lpr granulocytes but were suppressed by G-CSF treatment or Bcl-2 overexpression. Although activation of p38 MAPK has been implicated in granulocyte death, their apoptosis actually was markedly accelerated by specific inhibitors of this kinase. These results suggest that G-CSF promotes granulocyte survival largely through the Bcl-2–controlled pathway, whereas CD95 regulates a distinct pathway to apoptosis that is not required for either their spontaneous or drug-induced death. Moreover, p38 MAPK signaling contributes to granulocyte survival rather than their apoptosis.

Bibliography

Villunger, A., OâReilly, L. A., Holler, N., Adams, J., & Strasser, A. (2000). FAS Ligand, Bcl-2, Granulocyte Colony-Stimulating Factor, and p38 Mitogen-Activated Protein Kinase. The Journal of Experimental Medicine, 192(5), 647â658.

Authors 5

Andreas Villunger (first)
Lorraine A. O'Reilly (additional)
Nils Holler (additional)
Jerry Adams (additional)
Andreas Strasser (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:48 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 6:44 a.m.)
Indexed	3 months, 1 week ago (May 18, 2025, 12:22 p.m.)
Issued	25 years ago (Aug. 28, 2000)
Published	25 years ago (Aug. 28, 2000)
Published Online	25 years ago (Aug. 28, 2000)
Published Print	24 years, 11 months ago (Sept. 5, 2000)

Funders 0

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BibTeX

@article{Villunger_2000, title={FAS Ligand, Bcl-2, Granulocyte Colony-Stimulating Factor, and p38 Mitogen-Activated Protein Kinase}, volume={192}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.192.5.647}, DOI={10.1084/jem.192.5.647}, number={5}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Villunger, Andreas and O’Reilly, Lorraine A. and Holler, Nils and Adams, Jerry and Strasser, Andreas}, year={2000}, month=aug, pages={647–658} }

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