When bone marrow is examined in a smear, platelet fields are seen to fill much of the peripheral cytoplasm of the megakaryocyte. When examined with the TEM, the peripheral cytoplasm of the megakaryocyte appears to be divided into small compartments by invagination of the plasma membrane. As described above, these invaginations are the platelet demarcation channels (see Fig. 10.13). Thrombocytopenia (a low blood platelet count) is an important clinical problem in the management of patients with immune-system disorders and cancer (i.e., leukemia). It increases the risk of bleeding and in cancer patients often limits the dose of chemotherapeutic agents.
Development of Granulocytes (Granulopoiesis)
Granulocytes originate from the multipotential common myeloid progenitor (CMP) stem cell, which differentiates into granulocyte/monocyte progenitors (GMPs) under the influence of cytokines such as GM-CSF, granulocyte colony-stimulating factor (G-CSF), and IL-3. GM-CSF is a cytokine secreted by endothelial cells, T cells, macrophages, mast cells, and fibroblasts. It stimulates GMP cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. The neutrophil progenitor (NoP) undergoes six morphologically identifiable stages in the process of maturation: myeloblast, promyelocyte, myelocyte, metamyelocyte, band cell, and mature neutrophil. Eosinophils and basophils undergo a morphologic maturation similar to that of neutrophils. GMP cells, when induced by GM-CSF, IL-3, and IL-5, differentiate to eosinophil progenitors (EoPs), and eventually mature to eosinophils. Lack of IL-5 causes the GMP cells to differentiate into basophil progenitors (BaPs), which produce basophils. One cannot differentiate eosinophilic or basophilic precursors from neutrophilic precursors morphologically in the light microscope until the cells reach the myelocytic stage when the specific granules appear.
Myeloblasts are the first recognizable cells that begin the process of granulopoiesis.
The myeloblast is the earliest microscopically recognizable neutrophil precursor cell in the bone marrow. It has a large, euchromatic, spherical nucleus with three to five nucleoli. It measures 14 to 20 m in diameter and has a large nuclear-tocytoplasmic volume. The small amount of agranular cytoplasm stains intensely basophilic. A Golgi area is often seen where the cytoplasm is unstained. The myeloblast matures into a promyelocyte.
Promyelocytes are the only cells to produce azurophilic granules.
The promyelocyte has a large spherical nucleus with azurophilic (primary) granules in the cytoplasm. Azurophilic granules are produced only in promyelocytes; cells in subsequent stages of granulopoiesis do not make azurophilic granules. For this reason, the number of azurophilic granules is reduced with each division of the promyelocyte and its progeny. Promyelocytes do not exhibit subtypes. Recognition of the neutrophil, eosinophil, and basophil lines is possible only in the next stage—the myelocyte—when specific (secondary) and tertiary granules begin to form.
Myelocytes first exhibit specific granules.
Myelocytes begin with a more or less spherical nucleus that becomes increasingly heterochromatic and acquires a distinct indentation during subsequent divisions. Specific granules begin to emerge from the convex surface of the Golgi apparatus, whereas azurophilic granules are seen at the concave side. The significance of this separation is unclear. Myelocytes continue to divide and give rise to metamyelocytes.