IL-4Rα, a New Member that Associates with Syk Kinase: Implication in IL-4-Induced Human Neutrophil Functions

Although Syk has been reported to be associated with IL-2R alpha and IL-15R alpha in some hematopoietic cells, its association has never been investigated in the IL-4/IL-4R system. In this study, we demonstrate for the first time that Syk is constitutively associated with IL-4R alpha in human polymorphonuclear neutrophils (PMNs) and that IL-4 stimulation increases the amount of Syk associated with IL-4R alpha. Moreover, upon IL-4 treatment, a pool of Syk associated with IL-4R alpha is phosphorylated. We also report that such association is not unique to PMNs because Syk associates with IL-4R alpha in Raji and in PBMC cells. Stimulation of PMNs by IL-4 increased the amount of Syk associated with PLC-gamma 2, pAkt, and a-tubulin. Pretreatment of cells with the Syk-selective inhibitor piceatannol or Syk inhibitor II, significantly inhibited the ability of IL-4 to enhance phagocytosis and cell adhesion and to delay apoptosis, and these results correlate with the ability of piceatannol to reduce Syk activation and its association with IL-4R alpha. Down-regulation of Syk by antisense techniques demonstrates the importance of Syk in the antiapoptotic effect of IL-4. We conclude that association of Syk to IL-4R alpha is of biological significance and that IL-4R alpha is a new candidate to be added to the few cytokine receptor components which associate with Syk. The Journal of Immunology, 2009, 183: 5261-5269.