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.
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 FcvarepsilonRI. 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 FcvarepsilonRI 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 FcvarepsilonRI 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 FcvarepsilonRI activation depends on the relative levels of pro- and antiapoptotic Bcl-2 family members.
Alfredsson
J
J
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
Puthalakath
H
H
Martin
H
H
Strasser
A
A
Nilsson
G
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000172:deficiency; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011940:Receptor Aggregation / Q000502:physiology; D017455:Receptors, IgE / Q000378:metabolism / Q000502:physiology*; D019089:Stem Cell Factor / Q000172:deficiency; D015854:Up-Regulation; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C494812:Bcl2l1 protein, mouse; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D016207:Cytokines; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE; D019089:Stem Cell Factor; D051020:bcl-X Protein; D007073:Immunoglobulin E; D019009:Proto-Oncogene Proteins c-kit