期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 391, 期 4, 页码 1714-1720出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.12.139
关键词
Mast cells; Allergy; IgE receptor; Fyn kinase; Calcium; Degranulation; IL-2
资金
- Conacyt [83079]
IgE-antigen-dependent crosslinking of the high affinity IgE receptor (Fc epsilon RI) on mast cells leads to degranulation, leukotriene synthesis and cytokine production. Calcium (Ca2+) mobilization is a sine qua non requisite for degranulation, allowing the rapid secretion of stored pro-inflammatory mediators responsible for allergy symptoms. Fyn is a Src-family kinase that positively controls Fc epsilon RI-induced mast cell degranulation. However, our understanding of the mechanism connecting Fyn activation to secretion of pre-synthesized mediators is very limited. We analyzed Fc epsilon RI-dependent Ca2+ mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular Ca2+ influx after Fc epsilon RI crosslinking but not after thapsigargin addition. High concentrations of Gadolinium (Gd3+) partially blocked Fc epsilon RI-induced Ca2+ influx in WT cells but, in contrast, completely inhibited Ca2+ mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the canonical transient receptor potential (TRPC) Ca2+ channels (2-aminoethoxyphenylborane, 2-APB) blocked Fc epsilon RI-induced maximal Ca2+ rise in WT but not in Fyn -/- cells. Ca2+ entry through Fyn-controlled, 2-APB sensitive channels was found to be important for full degranulation and IL-2 mRNA accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its association is not related to protein tyrosine phosphorylation. Results indicate Fyn kinase mediates the receptor-dependent activation of TRPC channels that contribute to degranulation in Fc epsilon RI-stimulated mast cells. (C) 2009 Elsevier Inc. All rights reserved.
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