Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation

Zou Xiang, Ahmed A. Ahmed, Christine Möller, Kei Ichi Nakayama, Shigetsugu Hatakeyama, Gunnar Nilsson

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Mast cells reside in tissues, where upon activation through the high-affinity-IgE-receptor (FcΕRI) they degranulate and orchestrate the allergic reaction. Mast cells survive this activation and can thus be reactivated. In this study we demonstrate that this process depends on the prosurvival gene Al. Activation of mast cells through FcΕRI resulted in degranulation, strong induction of A1 mRNA and protein, and cell survival. In contrast, Al-deficient mast cells released granule mediators similar to the wild-type control, but the cells did not survive an allergic activation. Furthermore, A1-/- mice that had been sensitized and provocated with allergen exhibited a lower number of mast cell compared with littermate controls. The induction of A1 was dependent on calcium, as EDTA prevented A1 expression. The calcium ionophore, ionomycin, induced A1 expression and mast cell survival, whereas compound 48/80, a well-known mast cell secretagogue, did not. This study uncovers the importance of A1 for mast cell survival in allergic reactions, and it proposes A1 as a potential target for the treatment of allergic diseases.

Original languageEnglish
Pages (from-to)1561-1569
Number of pages9
JournalJournal of Experimental Medicine
Volume194
Issue number11
DOIs
Publication statusPublished - Dec 3 2001

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Mast Cells
Cell Survival
Hypersensitivity
p-Methoxy-N-methylphenethylamine
IgE Receptors
Ionomycin
Calcium Ionophores
BCL2-related protein A1
Edetic Acid
Allergens
Transcriptional Activation
Calcium
Messenger RNA
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation. / Xiang, Zou; Ahmed, Ahmed A.; Möller, Christine; Nakayama, Kei Ichi; Hatakeyama, Shigetsugu; Nilsson, Gunnar.

In: Journal of Experimental Medicine, Vol. 194, No. 11, 03.12.2001, p. 1561-1569.

Research output: Contribution to journalArticle

Xiang, Zou ; Ahmed, Ahmed A. ; Möller, Christine ; Nakayama, Kei Ichi ; Hatakeyama, Shigetsugu ; Nilsson, Gunnar. / Essential role of the prosurvival bcl-2 homologue A1 in mast cell survival after allergic activation. In: Journal of Experimental Medicine. 2001 ; Vol. 194, No. 11. pp. 1561-1569.
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