Requirement of Lyn and Syk tyrosine kinases for the prevention of apoptosis by cytokines in human eosinophils

被引:203
作者
Yousefi, S
Hoessli, DC
Blaser, K
Mills, GB
Simon, HU
机构
[1] UNIV ZURICH,SWISS INST ALLERGY & ASTHMA RES,CH-7270 DAVOS,SWITZERLAND
[2] UNIV GENEVA,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND
[3] UNIV TEXAS,MD ANDERSON CANC CTR,DIV MED,HOUSTON,TX 77030
关键词
D O I
10.1084/jem.183.4.1407
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In allergic diseases, the cytokines interleukin (IL)5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are upregulated and have been proposed to cause blood and tissue eosinophilia by inhibition of eosinophil apoptosis. We demonstrate herein, in freshly isolated human eosinophils, that the IL-3/IL-5/GM-CSF receptor beta subunit interacts with cytoplasmic tyrosine kinases to induce phosphorylation of several cellular substrates, including the beta subunit itself. The Lyn and Syk intracellular tyrosine kinases constitutively associate at a low level with the IL-3/IL-5/GM-CSF receptor beta subunit in human eosinophils. Stimulation with GM-CSF or IL-5 results in a rapid and transient increase in the amount of Lyn and Syk associated with the IL-3/IL-5/GM-CSF receptor beta subunit. Lyn is required for optimal tyrosine phosphorylation and activation of Syk. In contrast, Syk is not required for optimal tyrosine phosphorylation and activation of Lyn. These data suggest that Lyn is proximal to Syk in a tyrosine kinase cascade that transduces IL-3, IL-5, or GM-CSF signals. Compatible with this model, both Lyn and Syk are essential for the activation of the antiapoptotic pathway(s) induced through the IL-3/IL-5/GM-CSF receptor beta subunit in human eosinophils.
引用
收藏
页码:1407 / 1414
页数:8
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