Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to FcgammaR activation.
The tyrosine kinase Syk has been proposed to play a critical role in the antiapoptotic effect of interleukin (IL)-5 in human eosinophils. However, little is known about the involvement of Syk in other IL-5-mediated activation events. To further address these questions, the role of Syk in IL-5-induced eosinophil differentiation, activation, and survival was analyzed using cells obtained from Syk-deficient mice. We could demonstrate that Syk-deficient fetal liver cells differentiate into mature eosinophils in response to IL-5 at the same rate as wild-type fetal liver cells and generate the same total number of eosinophils. Moreover, no difference in IL-5-induced survival of mature eosinophils between Syk(-/-) and wild-type eosinophils could be demonstrated, suggesting that the antiapoptotic effect of IL-5 does not require Syk despite the activation of this tyrosine kinase upon IL-5 receptor ligation. In contrast, eosinophils derived from Syk-deficient but not wild-type mice were incapable of generating reactive oxygen intermediates in response to Fcgamma receptor (FcgammaR) engagement. Taken together, these data clearly demonstrate no critical role for Syk in IL-5-mediated eosinophil differentiation or survival but underline the importance of this tyrosine kinase in activation events induced by FcgammaR stimulation.
Lach-Trifilieff
E
E
Novartis Horsham Research Centre, Horsham, England; and National Institute for Medical Research, London, England.
Menear
K
K
Schweighoffer
E
E
Tybulewicz
V L
VL
Walker
C
C
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002470:Cell Survival; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000172:deficiency* / Q000502:physiology; D004804:Eosinophils / Q000166:cytology / Q000201:enzymology*; D015848:Interleukin-5 / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D016897:Respiratory Burst; D000072377:Syk Kinase
D004792:Enzyme Precursors; D015848:Interleukin-5; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D011961:Receptors, Fc; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse