A model for STAT3 function in neutrophil mobilization. Neutrophils are retained in the bone marrow in part through their expression of CXCR4, which interacts with SDF-1 expressed by stromal cells. G-CSF treatment directly or indirectly down-regulates CXCR4 and SDF-1; repression of SDF-1 requires STAT3 (dashed line). G-CSF treatment also induces the neutrophil chemoattractants KC and MIP-2 in the bone marrow (dashed line), as well as concurrent up-regulation of their shared receptor CXCR2 on the surface of neutrophils (solid line); induction of KC, MIP-2 and CXCR2 each require STAT3. STAT3 also controls the amplitude of MIP-2-induced Raf/MEK/ERK signaling (dashed line), which is crucial for neutrophil chemotaxis. Solid line denotes direct molecular regulation by STAT3; dashed lines indicate STAT3 regulation may be direct or indirect.