regulated by expression of C/EBPα, which is necessary for the transition from CMPs to GMPs and levels of PU.1, that drive the differentation from GMPs to monocytes (high PU.1 levels) or to granulocytes (low PU.1 levels). Committed granulopoiesis is regulated by C/EBPε and GFI-1, these two transcriptional factors are important for terminal granulocyte differentiation. Other transcriptional factors that regulate granulopoiesis are: CBF, MYB, SMAD4 and HOX genes. Regulation by cytokines Granulopoiesis is also regulated by cytokines to a certain extent. The main cytokines driving granulopoiesis are: GM-CSF (formation of GMPs from CMPs), G-CSF (commitment to the granulocyte lineage, formation of myeloblasts from GMPs), IL-3 (enhances the production of GM-CSF and G-CSF) and SCF. These are secreted by other haematopoietic cells in the bone marrow or at the site of inflammation as well as epithelial and endothelial cells. Types of granulopoiesis Steady state granulopoiesis Steady state granulopoiesis is a term used to describe the normal daily production of granulocytes. Granulocytes are short lived cells (their lifespan is between 6 and 8 hours) with a high cell turnover. The number of granulocytes produced every day is between 5 and 10 x 1010. The master regulator of steady state granulopoiesis is C/EBPα. It restricts the cell cycle of immature cells by inhibition of CDK2 and CDK4 and promotes granulocytic differentiation. Steady state production of granulocytes is activated after the engulfment of apoptotic granulocytes by tissue macrophages. Emergency granulopoiesis Steady state granulopoiesis is switched to a program termed emergency granulopoiesis after a major insult to the organism, usually a bacterial infection. The switch of the program is mediated by switch from C/EBPα to C/EBPβ, the main transcriptional regulator of emergency granulopoiesis. C/EBPβ enhances the production of granulocytes by promoting progression of the cell cycle of myeloid progenitors at accelerated rate, therefore generating sufficient amount of new granulocyte to fight the insult. References Hematopoiesis