Question

Identify mechanisms that modulate granulopoiesis.

Answer 1

Granulopoiesis begins when the myeloblast differentiates into a neutrophilic promyelocyte that is irreversibly committed to the neutrophilic cell line. Promyelocyte is large cells with purple-staining nonspecific azurophilic granules. Promyelocytes develop into myelocytes that are characterized by the presence of smaller specific or secondary granules. During this stage the number of specific granules per cell increases and the number of azurophilic granules per cell decreases, resulting in a loss of cytoplasmic basophilia. Granule production ceases at the end of the myelocyte stage and the remaining stages are characterized primarily by a reduction in cell size and a change in nuclear shape. When the nucleus becomes flattened and the chromatin further condensed, the cell is called a metamyelocyte. When the nucleus becomes horseshoe-shaped, it is called a band cell. The cell is considered a mature neutrophil when the nucleus becomes segmented into lobes.

Granulopoiesis is regulated by four principal colony-stimulating factors that were initially identified in colony-forming assays. The four factors are interleukin-3 (IL-3), stem cell factor (SCF) or kit ligand, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF). These factors are released from activated T-lymphocytes, monocytes, and endothelial cells at the site of infection to stimulate granulopoiesis. T-cells also release IL-5, which is important for the terminal maturation of eosinophils and basophils. Myeloblasts, promyelocytes, and myelocytes are stimulated to proliferate by the colony-stimulating factors. Metamyelocytes, band and segmented mature granulocytes generally do not divide to produce further progeny. Granulocytes released into the circulation migrate into tissues where they act as phagocytes that neutralize invading organisms by generating reactive oxygen species and by releasing their granule contents into the phagosome.

The neutrophil granulocytes are derived, in the present state of our knowledge, from a hemocytoblast identical with that of the other blood cells, defined by its power to form in vivo clones of multiple compositions, defining their characteristic of the totipotential undifferentiated cell. The way in which the clone-forming cell evolves in vivo towards granulopoiesis depends on a genetic factor, phenomena of derepression and an extrinsic factor, the origin of which is probably cellular. Differentiation of the hemocytoblast leads to a cell, the destiny of which is then fixed, which may then form clones in vitro in semi-solid medium (clone-forming cell in vitro or CFC). This cell is definitely a true entity. A humoral factor of macrophage origin intervenes to ensure granulopoiesis in vivo (clone-stimulating factor CSF3.