Control of myeloid-specific integrin alpha Mbeta 2 (CD11b/CD18) expression by cytokines is regulated by Stat3-dependent activation of PU.1

Granulocyte colony-stimulating factor (G-CSF) plays an essential role in regulating multiple aspects of hematopoiesis. To elucidate the role of G-CSF in controlling hematopoietic cell migration capabilities, we studied inducible expression of the myeloid-specific marker, integrin alpha(M)beta(2) (CD11b/CD18, Mac-1), in the myeloid cell line, 32D. We found that G-CSF stimulates the synthesis and cell surface expression of alpha(M) and beta(2) integrin subunits. Induction of both alpha(M) and beta(2) is dependent on Stat3, a major G-CSF-responsive signaling protein. However, the kinetics of expression suggested the involvement of an intermediate protein regulated by Stat3. Our results demonstrate that Stat3 signaling stimulates the expression of PU.1, a critical regulator of myelopoiesis. Furthermore, we show that PU.1 is an essential intermediate for the inducible expression of alpha(M)beta(2) integrin. Thus, Stat3 promotes alpha(M)beta(2) integrin expression through its activation of PU.1. These findings indicate that G-CSF-dependent Stat3 signals stimulate the changes in cell adhesion and migration capabilities that occur during myeloid cell development. These data also demonstrate a link between Stat3 and PU.1, suggesting that Stat3 may play an instructive role in hematopoiesis.