ANTI-APOPTOTIC SIGNALS OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ARE TRANSDUCED VIA JAK2 TYROSINE KINASE IN EOSINOPHILS

Cytokine-mediated inhibition of eosinophil apoptosis is a mechanism ca using tissue eosinophilia. Previously published work suggested that ac tivation of the Lyn-Ras-Raf-1-MAP kinase pathway is obligatory for pre vention of eosinophil apoptosis by eosinophil hematopoietins. We demon strate herein that activation of freshly isolated human blood eosinoph ils by granulocyte-macrophage colony-stimulating factor (GM-CSF) is as sociated with increased tyrosine phosphorylation of Jak2. The tyrosine kinase blocker, tyrphostin B42, prevented activation of Jak2 but not Lyn, suggesting that Jak2 is the specific target for tyrphostin B42 in eosinophils. In addition, since Lyn remained unaffected by tyrphostin B42, it is unlikely that Jak2 is required for Lyn activation in this model. To test whether tyrosine phosphorylation of Jak2 is linked to G M-CSF-mediated prolonged eosinophil survival, we determined the effect of tyrphostin B42 on eosinophil viability and apoptosis. Prevention o f Jak2 activation by tyrphostin B42 was associated with the inability of GM-CSF to prevent eosinophil apoptosis. These data suggest that dis ruption of not only the Lyn-Ras-Raf-1-MAP kinase but also the Jak-STAT pathway blocks the ability of eosinophil survival factors to prevent apoptosis in eosinophils.