Hemopoiesis
The various different kinds of blood cells have a finite life span in the circulation. Red blood cells last for about 120 days, platelets for 10 days and granulocytes can live for less than 24 hours. Monocytes only circulate from one to three days, but later migrate to the tissue to become the longer-lived macrophages. All these cells are continually replaced by the generative process called hemopoiesis.
Hemopoiesis is an extremely active process. In the adult human, approximately 1010 red blood cells and 4 x 108 white blood cells are produced per day. The principal site of hemopoiesis in the adult is the red marrow within bones, which occupies the medullary cavities of long bones and interstices in the spongiosa of vertebrae, ribs and sternum. Bone marrow occurs in two forms: red marrow, which is active in hemopoiesis, and yellow marrow, which is inactive and consists mainly of adipose cells, giving it its yellow color. Active red marrow is a soft, highly cellular tissue consisting of the precursors of blood cells supported by a stroma of reticular cells and associated reticular fibers. The reticular cells synthesize the collagen of the stromal reticular fibers. They, as well as the macrophages of the marrow, are believed to release cytokines, called colony-stimulating factors (CSFs), which promote proliferation and differentiation of the blood cell precursors. In the embryo, before bone marrow develops, blood cells are produced in the yolk sac during early embryonic life and in the fetal liver during the second trimester of pregnancy.
Blood cell formation depends on the existence of hemopoietic precursor cells in the bone marrow. All the cell types in mature blood are generated from such single pluripotential stem cells. These stem cells have the capacity to proliferate indefinitely and differentiate into many cell types. They can divide to renew themselves in order to maintain the pool pluripotential cell pool, while at the same time generating cells that become committed to developing into the various blood cell lines. First the stem cells divide to become either lymphoid or myeloid precursors. The lymphoid precursors migrate to lymphoid tissues, where they divide and differentiate into B and T lymphocytes. The mixed myeloid precursors remain in the bone marrow. There they divide further and their daughter cells become committed to producing one of the several types of blood cells, i.e., over several divisions they become unipotential cells. Sometimes, specific names are given to the development of particular cell lines. For example, erythropoiesis is the process of red blood cell formation from proerythroblasts which are large, early cells committed to erythrocyte development. Also granulopoiesis is the formation of granulocytes from the myeloblast cells. Thrombopoiesis is the formation of blood platelets, or thrombocytes, the cellular elements that promote blood clotting. Platelets are generated in the bone marrow by fragmentation of the cytoplasm of mature megakaryocytes. Like red blood cells, blood platelets lack nuclei.
The cells in the early stages of hemopoietic development are generally larger than those in more advanced, later stages. As they become committed to developing into one particular cell line, they express only the genes characteristic of that line. In some lines, they stop transcribing genes altogether. Morphological changes accompany this commitment and include a visible decrease in nuclear euchromatin and increase in heterochromatin. Also, ribosomes are most actively produced in the early stages of differentiation and decrease gradually as the cells become committed.
Pluripotential hemopoietic cells are relatively few in number (1 out of 10,000). The evidence for their existence came from experiments with bone marrow transplantation. Mice were irradiated to destroy their own bone marrow and were transfused with the bone marrow of healthy mice. Two weeks later, the spleens of the transfused mice were examined and found to contain colonies of cells resulting from the proliferation of the newly transfused cell type. Each colony was found to contain precursors to all the different blood cells present in peripheral blood. When isolated single colonies were further transfused into irradiated mice, each gave rise to several colonies, all containing cells of all the different lineages. These studies showed that one pluripotential cell forming one colony can give rise to all the lines of cells differentiating into the various blood cells. Because they are studied in the spleen colony assay, hematopoietic precursors are sometimes called colony forming units, or CFUs. As the pluripotential cells become committed, it is possible to distinguish progenitor cells of 4 kinds: (1) colony-forming unit granulocyte-monocyte (CFU-GM), (2) colony-forming unit erythrocyte (CFU-E), (3) colony-forming unit lymphocyte (CFU-L) and (4) colony-forming unit megakaryocyte (CFU-Me).
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