[Physiological (programmed) cell death in hemopoiesis]

According to current concepts, pluripotent cells proliferate and differentiate into "committed" precursors. These committed precursors divide, mature, and give rise to red cells, granulocytes, monocytes, and platelets of the blood. The life span of mature circulating cells being short, and their populations in the blood very stable, a constant and strict regulation of hematopoiesis is needed. The regulation of hematopoiesis is believed to be mediated through precursor cell interaction with specific molecules (glycoproteins) in their microenvironment. Soluble forms of these molecules are termed "hematopoietic growth factors" and include erythropoietin, colony-stimulating factors, interleukins, and stem cell factors. Hematopoietic growth factors not only stimulate the proliferation of precursor cells, but activate the differentiation program and maintain the viability of these cells as well. The normal fate of precursor cells devoid of these factors is programmed suicide. The morphology of such cell death is usually that of apoptosis, rather than of necrosis. The concept of apoptosis was proposed 22 years ago. Apoptosis is a widespread and morphologically distinct process of cell death. The significance of apoptosis stems from its active nature and its ability of controlling biological systems. The present review of published and authors' own data describes apoptosis morphology and presents evidence of the participation of cell reactions of this type in hematopoiesis regulation. The major point in the review is the balance of three normal processes: proliferation, differentiation, and apoptosis, which maintains the homeostasis of hematopoiesis, similarly as of any other cell system; it is well illustrated by recent findings in experimental and clinical hematology.