Systems approach to phagocyte production and activation: neutrophils and monocytes

Granulocyte differentiation and immune response function is a dynamic process governed by a highly coordinated transcriptional program that regulates cellular fate and function, often in a context-dependent manner. Advances in high-throughput technologies and bioinformatics have allowed us to better understand complex biological processes at the genomic and proteomic levels. Components of the environmental milieu, along with the molecular mechanisms that drive the development, activation, and regulation of granulocytes, have since been elucidated. In this chapter, we present the intricate network in which these elements come together and influence one another. In particular, we describe the critical roles of transcription factors like PU.1, CCAAT/enhancer-binding protein (C/EBPα; alpha), C/EBPε (epsilon), and growth factor independent-1 (Gfi-1). We also review granulocyte colony-stimulating factor (G-CSF) receptor-induced signal transduction pathways, their influence on proliferation and differentiation, and the cooperativity of cytokines and chemokines in this process.