Background: The contribution of mast cells to the pathology of allergic diseases are facilitated by their long life span in tissue and ability to regranulate. Bcl-2 genes are one of the main regulators of cell death and survival. The aim of this study was to elucidate the mechanisms responsible for mast cell survival in allergy. Methods: Bcl-2 family gene expression in human mast cells and basophils was analyzed by ribonuclease protection assay and by reverse-transcriptase polymerase chain reaction. Cell survival was measured by mixing cells with the vital dye, trypan blue, and the number of living cells was enumerated. Apoptotic cells were measured by a Cell Death Detection ELISA. Results: We found that cross-linking of FcεRI on human cord blood cultured mast cells (CBCMCs) promoted cell survival and induced expression of the pro-survival gene Bfl-1. CBCMCs were found to express both Bfl-1 and Bfl-1S, two splicing variants of Bfl-1. Bfl-1 induction was mediated through Syk, PI3-kinase and intracellular calcium mobilization, since piceatannol, wortmannin and EDTA, respectively, significantly reduced Bfl-1 expression levels. In contrast to CBCMCs, no evidence was found for Bfl-1 expression and survival promotion in human basophils. Conclusions: Immunoglobulin E (IgE)-dependent activation-induced mast cell survival was correlated with Bfl-1 gene upregulation, providing a possible explanation for mast cell longevity in allergic reactions.
|Number of pages||7|
|Journal||Allergy: European Journal of Allergy and Clinical Immunology|
|Publication status||Published - 1 Sep 2006|
- Bcl-2 family members
- Mast cell
ASJC Scopus subject areas