Hematopoietic Homeostasis Involves Many Factors

Hematopoiesis is a continuous process that generally maintains a steady state in which the production of mature blood cells equals their loss (principally from aging). The average erythrocyte has a life span of 120 days before it is phagocytosed and digested by macrophages in the spleen. The various white blood cells have life spans ranging from a few days, for neu-trophils, to as long as 20-30 years for some T lymphocytes. To maintain steady-state levels, the average human being must produce an estimated 3.7 X 1011 white blood cells per day.

Hematopoiesis is regulated by complex mechanisms that affect all of the individual cell types. These regulatory mechanisms ensure steady-state levels of the various blood cells, yet they have enough built-in flexibility so that production of blood cells can rapidly increase tenfold to twentyfold in response to hemorrhage or infection. Steady-state regulation of hematopoiesis is accomplished in various ways, which include:

■ Control of the levels and types of cytokines produced by bone-marrow stromal cells

■ The production of cytokines with hematopoietic activity by other cell types, such as activated T cells and macrophages

■ The regulation of the expression of receptors for hematopoietically active cytokines in stem cells and progenitor cells

■ The removal of some cells by the controlled induction of cell death

A failure in one or a combination of these regulatory mechanisms can have serious consequences. For example, abnormalities in the expression of hematopoietic cytokines or their receptors could lead to unregulated cellular proliferation and may contribute to the development of some leukemias. Ultimately, the number of cells in any hematopoietic lineage is set by a balance between the number of cells removed by cell death and the number that arise from division and differentiation. Any one or a combination of regulatory factors can affect rates of cell reproduction and differentiation. These factors can also determine whether a hematopoietic cell is induced to die.

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