The size of the reserve pool in the bone marrow and in the vascular compartment depends on the rate of granulopoiesis, the life span of the neutrophils, and the rates of migration into the bloodstream and connective tissue. The entire hemopoietic process is summarized in Table 10.3.
Transcription factors control the fate of hemopoietic cells, whereas cytokines and local mediators regulate all stages of hemopoiesis.
Intimate interactions between HSCs and their bone marrow microenvironment work toward redefining the identity and the differentiation pathways of these multipotential stem cells. Signaling molecules from a variety of bone marrow cells initiate intracellular pathways that ultimately target a select group of synergistic and inhibitory proteins known as transcription factors. They specifically bind to promoter or enhancer regions on DNA in the affected cell. By controlling transcription of the specific genes downstream, these transcription factors trigger a cascade of genetic changes that ultimately determines the course of the cells during differentiation. In addition to identifying the various intracellular transcription factors, recent studies have identified and begun to characterize numerous signaling molecules found in the bone marrow. These include glycoproteins that act as both circulating hormones and local mediators to regulate the progress of hemopoiesis and the rate of differentiation of other cell types (Table 10.4). Specific hormones such as erythropoietin or thrombopoietin, discussed in a previous section, regulate erythrocyte and thrombocyte development, respectively. Other factors, collectively called colony-stimulating factors (CSFs), are subclassified according to the specific cell or group of cells that they affect. Among the recently isolated and most completely characterized factors are several that stimulate granulocyte and monocyte formation, GM-CSF, G-CSF, and macrophage colony-stimulating factor (M-CSF). Interleukins, produced by lymphocytes, act on other leukocytes and their progenitors. IL-3 is a cytokine that appears to affect most progenitor cells and even terminally differentiated cells. Any particular cytokine may act at one or more stages in hemopoiesis, affecting cell division, differentiation, or cell function. These factors are synthesized by many different cell types, including kidney cells (erythropoietin), liver hepatocytes (thrombopoietin), T lymphocytes (IL-3), endothelial cells (IL-6), adventitial cells in the bone marrow (IL-7), and macrophages (the CSFs that affect granulocyte and macrophage development).