Early Stages of Development: Promyelocytes and Myelocytes
The maturation of granulocytes originates from Class IV cells—myeloblasts, which transform into maturing forms (Class V cells).
The first morphologically recognizable cell along this pathway is the promyelocyte. It is characterized by a round nucleus and a basophilic (blue-staining) cytoplasm. A key event at this stage is the appearance of nonspecific azurophilic granules (primary granules) in the cytoplasm. Specificity is absent at this stage, making it visually impossible to determine whether the cell will become a neutrophil, eosinophil, or basophil. Promyelocytes divide actively.
The next stage is the myelocyte stage. The nucleus remains round, but secondary (specific) granules begin to form in the cytoplasm. It is at this exact point that cells clearly segregate into three parallel differentiation lines:
- Neutrophilic (synthesize and store antibacterial substances).
- Eosinophilic (contain major basic protein, histaminase, and oxidases).
- Basophilic (accumulate histamine and heparin).
Myelocytes represent the predominant pool of granulocytic lineage cells in the red bone marrow. It is crucial to remember that this is the final stage capable of mitotic division.
Postmitotic Maturation of Granulocytes
Upon completing the myelocyte stage, cells irreversibly lose their capacity for division and enter postmitotic maturation. This group comprises a strict sequence of cell forms: metamyelocytes, band cells, and finally, segmented granulocytes.
A shared feature of this entire group is the absence of mitotic activity and the progressive acquisition of an irregular nuclear shape. Mature forms and their immediate precursors (metamyelocytes) are capable of entering the peripheral blood.
Dynamics of Nuclear Shape Changes
As a cell progresses along the maturation pathway from a metamyelocyte to a fully mature form, its nucleus undergoes a series of predictable transformations:
- Metamyelocyte: The nucleus begins to indent on one side, adopting a characteristic kidney-bean shape.
- Band (stab) granulocyte: The nucleus elongates, turning into a thick, curved rod (sometimes resembling a horseshoe); however, constrictions are still absent at this stage.
- Segmented granulocyte: The nucleus finally divides into several lobes (segments) connected by thin strands. An exception is basophils—their nucleus barely segments, remaining only weakly lobulated.
Monocyte Development (Monocytopoiesis)
Parallel to granulocytopoiesis is the formation of agranulocytes, specifically monocytes. Their early precursor is the monoblast (Class IV), which differentiates into the promonocyte (Class V).
Unlike granulocytes, promonocytes are represented by a single cell type without subdivision into subtypes. Morphologically, they feature a large, round nucleus and a lack of granules. As a promonocyte matures into a mature monocyte, its nucleus becomes kidney-shaped, and fine granules (representing lysosomes) appear in the cytoplasm.
Other Hematopoietic Lineages
In addition to leukocytes, elements of other hematopoietic lineages develop from Class IV cells:
- Erythroid lineage: The basophilic erythroblast sequentially transforms into a polychromatophilic erythroblast, then an orthochromatic erythroblast (normoblast). This is followed by a reticulocyte and, finally, a mature erythrocyte (Class VI).
- Thrombocytic lineage: The promegakaryocyte matures into a giant megakaryocyte, from which platelets are subsequently shed.