Abstract
Mast cells play critical roles in the regulation of acute and chronic inflammations. Apoptosis is one of the mechanisms that limit and resolve inflammatory responses. Mast cell survival can be controlled by growth factors and activation of the IgE-receptor FcɛRI. Members of the Bcl-2 protein family are critical regulators of apoptosis and our study provides evidence that the proapoptotic BH3-only family member Bim is essential for growth factor deprivation-induced mast cell apoptosis and that Bim levels increase upon FcɛRI activation. Bim deficiency or Bcl-2 overexpression delayed or even prevented cytokine withdrawal-induced mast cell apoptosis in culture. The prosurvival protein Bcl-XL and the proapoptotic Bim were both induced upon FcɛRI activation. These results suggest that Bim and possibly also other BH3-only proteins control growth factor withdrawal-induced mast cell apoptosis and that the fate of mast cells upon FcɛRI activation depends on the relative levels of pro- and antiapoptotic Bcl-2 family members.
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Abbreviations
- BH:
-
Bcl-2 homology
- BMMC:
-
bone marrow-derived mast cell
- SCF:
-
stem cell factor
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Acknowledgements
We thank Drs. Philippe Bouillet, Alan Harris and Professors Jerry Adams, and Suzanne Cory for providing the bim−/− and vav-bcl-2 transgenic mice, Phillip Morgan for help in the production of SCF, Professors Craig Thompson, Stan Korsmeyer and Dr. Robin Anderson for antibodies, Professor Stephen Galli for C57 cells, and Professor Birgitta Heyman and Mrs. Imma Brogren for help with analyzing the concentration of IgE. This work was supported by grants from The Swedish Cancer Society, The Swedish Research Council, Goran Gustafsson's Foundation, King Gustav V's 80 years Foundation, Ollie and Elof Ericsson's Foundation, Anna Cederberg's Foundation, Knut and Alice Wallenberg's Foundation (all from Sweden), the NHMRC (Canberra), the Leukemia and Lymphoma Society of America and the Cancer Research Institute (New York).
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Alfredsson, J., Puthalakath, H., Martin, H. et al. Proapoptotic Bcl-2 family member Bim is involved in the control of mast cell survival and is induced together with Bcl-XL upon IgE-receptor activation. Cell Death Differ 12, 136–144 (2005). https://doi.org/10.1038/sj.cdd.4401537
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DOI: https://doi.org/10.1038/sj.cdd.4401537
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