Granulopoiesis Overview

Granulopoiesis Definition

• Granulopoiesis (or Myelopoiesis) is the process of proliferation, differentiation, and maturation of granulocytes within the bone marrow.
• Granulocytes develop from pluripotent hematopoietic stem cells.
• Pluripotent hematopoietic stem cells (PHSC) differentiate into granulocyte-monocyte colony-forming units (GM-CFU).
• GM-CFU then further differentiates into granulocyte colony-forming units (G-CFU).
• G-CFU undergo successive divisions and maturation stages to eventually create mature granulocytes.

Granulopoiesis Stages

• Granulopoiesis involves a continuous development process from myeloblast to mature granulocytes within the bone marrow.
• Each granulocyte type follows a similar developmental pathway (myeloblast, promyelocyte, myelocyte, metamyelocyte, band cell, mature granulocyte).
• Granulocytes become distinguishable at the myelocyte stage when specific granules appear.
• During maturation, the nucleus shrinks, chromatin condenses, and the shape of the nucleus changes significantly.
• Primary granules appear and disappear, while secondary granules emerge. The cell's size also changes.
• Myeloblasts, promyelocytes, and myelocytes undergo mitosis and have the capability to divide.
• Metamyelocytes and band cells are components of a maturation pool and do not divide.
• Segmented neutrophils are stored in the bone marrow and released into the circulation.
• The circulatory system divides into two parts: circulating and marginating pools.
• Marginating granulocytes adhere to the blood vessel endothelium.
• Some granulocytes are found in the spleen, while mature forms circulate in the blood and are transient to tissue.
• Granulocytes migrate from circulation into peripheral tissues via diapedesis.

Granulopoiesis Stages: Specific Cells

• Granulopoiesis is subdivided into six stages: myeloblast, promyelocyte, myelocyte, metamyelocyte, band cells, and mature granulocytes (neutrophils, eosinophils, basophils).

• Myeloblast: Large, round-to-oval cells, scanty basophilic cytoplasm, lacking granules. The myeloblast sometimes displays "Auer rods," which signifies a pathological and abnormal condition

• Promyelocyte: Slightly larger than myeloblasts (15-21 µm), moderate basophilic cytoplasm, and primary granules within the cytoplasm

• Myelocyte: Smaller than promyelocytes (12-18 µm), primary and some secondary granules, basophilic cytoplasm (fewer) and a darker staining nucleus with coarsely clumped chromatin

• Metamyelocyte: Smaller than myelocytes, the nucleus is indented in a kidney or horseshoe shape. Pinkish cytoplasm

• Band Cell: Nucleus is in a band shape, smaller than Metamyelocytes in size. Pinkish cytoplasm

• Segmented Neutrophils (Mature Granulocytes): The nucleus has multiple segments, the cytoplasm is abundant and pink, containing granules that are pinkish-colored secondary granules.

Granulocyte Characteristics

• Granules of each granulocyte type differ in staining characteristics due to varying content.
• Segmented neutrophil granules have antibacterial substances, like lysosomal hydrolases, lysozyme, and myeloperoxidase.
• Eosinophil granules lack lysozyme, and basophil granules contain heparin and histamine.

Granulopoiesis Regulation

• Growth factors are crucial in the proliferation, growth, and maturation of granulocytes.
• These factors include GM-CSF, G-CSF, IL-6, IL-11, IL-1, IL-3, and IL-5.
• Increased granulocyte and monocyte production is triggered when infection occurs.
• Stromal cells and T lymphocytes increase the production of growth factors in response to endotoxins and cytokines, such as IL-1 or tumor necrosis factor (TNF).

Monocyte Development

• Monoblasts are precursors to monocytes, which mature into macrophages.
• Monoblasts are large cells with a round nucleus, fine chromatin, and a prominent nucleolus. Cytoplasm can be agranular or have fine basophilic granules.
• Promonocytes are immature cells developing from monoblasts into monocytes.
• Promonocytes have a moderate amount of blue–gray cytoplasm, fine granules, and sometimes cytoplasmic vacuoles. Their nuclei are irregular, folded, and convoluted, with less condensed chromatin compared to mature monocytes.

Monocyte Function

• Monocytes are part of the immune system that defend against pathogens.
• Monocytes are produced in bone marrow and enter the bloodstream.
• They travel to various tissues (spleen, liver, lungs, bone marrow).
• They act as scavenger cells by ingesting bacteria and other substances, as well as eliminating infected cells.
• They play a role in tissue repair and influence adaptive immune responses.
• Monocytes have a large, kidney-shaped nucleus, pale greyish-blue cytoplasm, and reddish-blue granules.

Clinical Application of G-CSF

• G-CSF (granulocyte colony-stimulating factor) is a therapeutic agent used intravenously or subcutaneously to increase neutrophil counts.
• It's used after chemotherapy/radiotherapy, stem cell transplantation, myelodysplasia, aplastic anemia, and severe benign neutropenia.
• Short-acting G-CSF is given daily, while longer-acting types are given every 7-14 days.

This quiz covers the definition and stages of granulopoiesis, the process through which granulocytes are produced in the bone marrow. Learn about the differentiation of hematopoietic stem cells and the key stages involved in the maturation of granulocytes. Test your knowledge on the development pathways from myeloblast to mature granulocytes.