Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to Fc gamma R activation

The tyrosine kinase Syk has been proposed to play a critical role in the an tiapoptotic effect of interleukin (IL)-5 in human eosinophils. However, lit tle 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-induce d eosinophil differentiation, activation, and survival was analyzed using c ells obtained from Syk-deficient mice. We could demonstrate that Syk-defici ent 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 surviv al of mature eosinophils between Syk(-/-) and wildtype eosinophils could be demonstrated, suggesting that the antiapoptotic effect of IL-5 does not re quire 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 re sponse to Fc gamma receptor (Fc gamma R) engagement. Taken together, these data clearly demonstrate no critical role for Syk in IL-5-mediated eosinoph il differentiation or survival but underline the importance of this tyrosin e kinase in activation events induced by Fc gamma R stimulation. (Blood, 20 00;96:2506-2510) (C) 2000 by The American Society of Hematology.