The two classes of cells dedicated to phagocytosis, neutrophils and macrophages, develop from a common progenitor cell called a granulocyte/macrophage (GM) progenitor cell. Like the other granulocytes (eosinophils and basophils), neutrophils circulate in the blood for only a few hours before migrating out of capillaries into the connective tissues or other specific sites, where they survive for only a few days. They then die by apoptosis and are phagocytosed by macrophages. Macrophages, in contrast, can persist for months or perhaps even years outside the bloodstream, where they can be activated by local signals to resume proliferation.
At least seven distinct CSFs that stimulate neutrophil and macrophage colony formation in culture have been defined, and some or all of these are thought to act in different combinations to regulate the selective production of these cells in vivo. These CSFs are synthesized by various cell types—including endothelial cells, fibroblasts, macrophages, and lymphocytes—and their concentration in the blood typically increases rapidly in response to bacterial infection in a tissue, thereby increasing the number of phagocytic cells released from the bone marrow into the bloodstream.
The CSFs not only operate on the precursor cells to promote the production of differentiated progeny, they also activate the specialized functions (such as phagocytosis and target-cell killing) of the terminally differentiated cells. CSFs can be synthesized artificially and are now widely used in human patients to stimulate the regeneration of hematopoietic tissue and to boost resistance to infection.
the behavior of a hematopoietic Cell depends partly on Chance
CSFs are defined as factors that promote the production of colonies of differentiated blood cells. But precisely what effect does a CSF have on an individual hematopoietic cell? The factor might control the rate of cell division or the number of division cycles that the progenitor cell undergoes before differentiating; it might act late in the hematopoietic lineage to facilitate differentiation; it might act early to influence commitment; or it might simply increase the probability of cell survival (Figure 22–34). By monitoring the fate of isolated individual hematopoietic cells in culture, it has been possible to show that a single CSF, such as granulocyte/ 1.
Frequency of stem-cell division 2.
Probability of stem-cell death 3.
Probability that stem-cell daughter will become a committed progenitor cell of the given type 4.
Division cycle time of committed progenitor cell 5.
Probability of progenitor-cell death 6.
Number of committed progenitorcell divisions before terminal     differentiation 7.
Lifetime of differentiated cells macrophage CSF, can exert all these effects, although it is still not clear which are most important in vivo.
Studies in vitro indicate, moreover, that there is a large element of chance in the way a hematopoietic cell behaves—a reflection, presumably, of “noise” in the genetic control system, as discussed in Chapters 7 and 8. If two sister cells are taken immediately after a cell division and cultured apart under identical conditions, they frequently give rise to colonies that contain different types of blood cells or the same types of blood cells in different numbers. Thus, both the programming of cell division and the process of commitment to a particular path of differentiation seem to involve random events at the level of the individual cell, even though the behavior of the multicellular system as a whole is regulated in a reliable way. The sequence of cell fate restrictions shown earlier, in Figure 22–31, conveys the impression of a program executed with computer-like logic and precision. Individual cells may be more varied, quirky, and erratic, and may sometimes progress by other decision pathways from the stem-cell state toward terminal differentiation.
Regulation of Cell Survival is as important as Regulation of Cell proliferation