LAT is essential for FcεRI-mediated mast cell activation

被引：313
作者：
Saitoh, S
Arudchandran, R
Manetz, TS
Zhang, WG
Sommers, CL
Love, PE
Rivera, J
Samelson, LE
机构：
[1] NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA
[2] NIAMSD, Sect Chem Immunol, NIH, Bethesda, MD 20892 USA
[3] NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA
来源：
IMMUNITY | 2000年 / 12卷 / 05期
基金：
日本学术振兴会;
关键词：
D O I：
10.1016/S1074-7613(00)80204-6
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement of T cells. LAT is also expressed in platelets, NK, and mast cells. Although LAT-deficient mice contain normal numbers of mast cells, we found that LAT-deficient mice were resistant to IgE-mediated passive systemic anaphylaxis. LAT-deficient bone marrow-derived mast cells (BMMC) showed normal growth and development. Whereas tyrosine phosphorylation of Fc epsilon RI, Syk, and Vav was intact in LAT-deficient BMMCs following Fc epsilon RI engagement, tyrosine phosphorylation of SLP-76, PLC-gamma 1, and PLC-gamma 2 and calcium mobilization were dramatically reduced. LAT-deficient BMMCs also exhibited profound defects in activation of MAPK, degranulation, and cytokine production after Fc epsilon RI cross-linking. These results show that LAT plays a critical role in Fc epsilon RI-mediated signaling in mast cells.
引用
收藏
页码：525 / 535
页数：11
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