DIFFERENTIAL ACTIVATION OF FUNCTIONALLY DISTINCT STAT5 PROTEINS BY IL-5 AND GM-CSF DURING EOSINOPHIL AND NEUTROPHIL DIFFERENTIATION FROM HUMAN CD34(-CELLS() HEMATOPOIETIC STEM)

Interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating fac tor (GM-CSF) are important cytokines for the proliferation, differenti ation, and activation of myeloid lineages. The JAK/STAT pathway is one of the signaling pathways implicated in mediating biological response s induced by these cytokines, Previous studies have demonstrated that these cytokines predominantly activate an 80 kDa STAT5 isoform in matu re granulocytes, To better understand the role of STAT proteins during growth and differentiation of granulocytes, we evaluated differentiat ion of human CD34(+) hematopoietic stem cells ex vivo toward eosinophi ls and neutrophils, Bandshift experiments showed that in an early stag e of both differentiation pathways (14 days), the 94 kDa STAT5B protei n was activated by both IL-5 (eosinophil lineage) and GM-CSF (neutroph il lineage). However, during maturation of both lineages (days 21 and 28), increased expression of a functionally distinct 80 kDa STAT5 isof orm was observed, resulting in heterodimer DNA-binding complexes conta ining both the 94 and 80 kDa STAT5 proteins. The finding that function ally distinct isoforms of STAT5 are activated during the early and lat e differentiation stages of granulocytes suggests that they might be i nvolved in regulating different biological functions in these cells.