期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 38, 期 3, 页码 841-854出版社
WILEY
DOI: 10.1002/eji.200737597
关键词
anaphylaxis; degranulation; Fc epsilon RI; mast cells; SWAP-70
类别
资金
- NIAID NIH HHS [AI 049282, R01 AI049282-05, R01 AI049282-01A2, R01 AI049282] Funding Source: Medline
Mast cells, perhaps best known by their ability to trigger allergic reactions after stimulation through the Fc epsilon RI, 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 Fc epsilon RI-mediated degranulation, which can be restored by expression of exogenous wild-type SWAP-70, but less so if a phosphatidylinositol trisphosphate (PIP3) binding mutant is expressed. SWAP-70 itself supports inositol-3-phosphate and PIP3 production, the latter indicating a potential feedback from SWAP-70 towards PI3K. Fc epsilon RI-stimulated transcription and release of cytokines is controlled by SWAP-70. Key Fc epsilon RI 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 Fc epsilon RI signaling, important for the control of mast cell-dependent anaphylaxis.
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