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- Title
SWAP-70 regulates mast cell FcϵRI-mediated signaling and anaphylaxis.
- Authors
Sivalenka, Raja R.; Sinha, Manoj; Jessberger, Rolf
- Abstract
Mast cells, perhaps best known by their ability to trigger allergic reactions after stimulation through the FcϵRI, express the unusual phosphatidylinositol 3-kinase (PI3K)-dependent, Rac-binding protein SWAP-70. Here, we show that the IgE-mediated passive cutaneous and the systemic anaphylactic responses are strongly reduced in SWAP-70 mice. Cultured SWAP-70 immature bone marrow mast cells (BMMC) are also impaired in FcϵRI-mediated degranulation, which can be restored by expression of exogenous wild-type SWAP-70, but less so if a phosphatidylinositol trisphosphate (PIP) binding mutant is expressed. SWAP-70 itself supports inositol-3-phosphate and PIP production, the latter indicating a potential feedback from SWAP-70 towards PI3K. FcϵRI-stimulated transcription and release of cytokines is controlled by SWAP-70. Key FcϵRI signal transduction events like activation of LAT by phosphorylation, activation of Akt/PKB and of p38 MAP kinase are reduced in SWAP-70 BMMC, but ERK is strongly hyperactivated. Some requirements for SWAP-70 were apparent only under limited-strength signaling conditions. We suggest that SWAP-70 defines a new element of efficient mast cell activation upon FcϵRI signaling, important for the control of mast cell-dependent anaphylaxis.
- Publication
European Journal of Immunology, 2008, Vol 38, Issue 3, p841
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200737597