Granulopoiesis and Its Regulation PDF

GRANULOPOIESIS AND ITS REGULATION  DEFINITION Granulopoiesis/Myelopoiesis It is the process of proliferation, differentiation and maturation of granulocytes in the bone marrow  GRANULOPOIESIS Granulocytes arise from pluripotent hematopoietic stem cells....

GRANULOPOIESIS AND ITS REGULATION  DEFINITION Granulopoiesis/Myelopoiesis It is the process of proliferation, differentiation and maturation of granulocytes in the bone marrow  GRANULOPOIESIS Granulocytes arise from pluripotent hematopoietic stem cells. PHSC differentiate into granulocyte-monocyte colony forming unit (GM-CFU). This further differentiated into granulocyte colony forming unit (G-CFU). G-CFU pass through successive divisions and stages and ultimately form mature granulocytes.  GRANULOPOIESIS Proliferation and maturation of myeloid series in the bone marrow demonstrates a continuum of development from myeloblast to the most mature granulocytes. Each granulocytes follow the same pattern of development i.e. myeloblast, promyelocyte, myelocyte, metamyelocyte, band cell and mature granulocytes. Each granulocyte can be distinguished at myelocyte stage due to the appearance of specific granules.  GRANULOPOIESIS During maturation, there is reduction in nucleus volume, condensation of chromatin, change in nuclear shape, appearance and disappearance of primary granules, appearance of secondary granules, color changes and change in size of the cell. Myeloblast, promyelocyte and myelocyte; these cells undergo mitosis and have the capability of division.  GRANULOPOIESIS Metamyelocytes and band cells are the components of maturation pool. These cells do not divide. Segmented neutrophils stored in the bone marrow and are released in the circulation. The peripheral blood circulation is subsequently divided into two pools of equal size: the circulating and the marginating pools. The marginating granulocytes adhere to the endothelium of the blood vessels. Some granulocytes are additionally found in the spleen. Mature granulocytes in the peripheral blood are only in transit to their potential sites of action in the tissues. The movement of granulocytes from the circulating pool to the peripheral tissues occurs by a process called diapedesis.  STAGES OF GRANULOPOIESIS  STAGES OF GRANULOPOIESIS Morphologically Granulopoiesis is divided into 6 stages 1. Myeloblast 2. Promyelocyte 3. Myelocyte 4. Metamyelocyte 5. Band cells 6. Mature granulocytes (Neutrophils, eosinophils, basophils)  STAGES OF GRANULOPOIESIS 1. Myeloblast Size: Large (15-20 um), Shape: Round to oval, Cytoplasm: Color: Scanty basphilic Lack granules Auer rods, which are aggregates of fused lysosomes, may appear as red, needle-like crystalline cytoplasmic inclusions. These inclusions may appear alone or in groups. Auer rods are pathological, not normal, inclusions. Nucleus: Color: Radish purple Shape: Round to oval Chromatin Pattern: Open Nucleolus: 2-4 present  STAGES OF GRANULOPOIESIS 2. Promyelocyte Size: Large (15-21 um), Shape: Round to oval, Cytoplasm: Color: Moderate Basophilic Granule: Primary granules (and are rich in the enzymes myeloperoxidase and esterase Nucleus: Color: Radish purple Shape: Round to oval Chromatin Pattern: Coarse Nucleolus: May be present  STAGES OF GRANULOPOIESIS 3. Myelocyte Size: Large (12-18 um), Shape: Round to oval, Cytoplasm: Color: abundant Basophilic Granule: Primary + appearance of secondary granules The separate cell types—neutrophils, eosinophils, and basophils— become visibly recognizable at this stage. Neutrophilic granules are fine and stain a blue-pink color with Wright stain. Eosinophilic granules are larger than neutrophilic granules. These round or oval-shaped granules are orange. Basophilic granules have a dark blue-black color and a dense appearance. Nucleus: Color: Radish purple Shape: Round to oval Chromatin Pattern: Coarse Nucleolus: Absent  STAGES OF GRANULOPOIESIS 4. Metamyelocyte Size: Large (10-18 um), Shape: Round to oval Cytoplasm: Color: abundant Pinkish Granule: Primary + secondary granules Nucleus: Color: Dark purple Shape: Kidney/horse-shoe shaped Chromatin Pattern: Condensed Nucleolus: Absent  STAGES OF GRANULOPOIESIS 5. Band Cell Size: Large (10-18 um), Shape: Round to oval Cytoplasm: Color: abundant Pinkish Granule: Primary + secondary granules Nucleus: Color: Dark purple Shape: Horse-shoe shaped Chromatin Pattern: Condensed Nucleolus: Absent  STAGES OF GRANULOPOIESIS 6. Segmented Neutrophil Size: Large (10-18 um), Shape: Round to oval Cytoplasm: Color: Abundant Pink Granule: Pinkish Primary + secondary granules Nucleus: Color: Dark purple Shape: Segmented/multi lobes (2-5) Chromatin Pattern: Condensed Nucleolus: Absent  The granules of each cell type stain differently because their contents vary. The characteristics of these granules are as follows. The granules of segmented neutrophils are rich in various antibacterial substances, including lysosomal hydrolases, lysozyme, and myeloperoxidase. Eosinophilic granules differ from neutrophilic granules in that they lack lysozyme. These granules are of two types: Smaller round granules, Larger crystalline granules, Basophilic granules contain heparin and histamine. Mast cells have granules that have an enzyme content similar to those of the blood basophil.  Regulation of Granulopoiesis Growth factors essential for the proliferation, growth, development and maturation of granulocytes include granulocyte-monocyte colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin-6 (IL-6), IL-11, IL-1, IL-3 and IL-5. Increased granulocyte and monocyte production in response to an infection is induced by increased production of growth factors from stromal cells and T lymphocytes, stimulated by endotoxin, and cytokines such as IL‐1 or tumor necrosis factor (TNF)  Regulation of Granulopoiesis  Regulation of Granulopoiesis Production and development of monocytes A monoblast is a type of cell that is a precursor to monocytes, which are a type of cell that matures into macrophages: Appearance Monoblasts are large cells with a round nucleus, fine chromatin, and a large nucleolus. They have a generous amount of cytoplasm that can be agranular or contain fine basophilic granules. A promonocyte is an immature cell that is in the process of developing from a monoblast into a monocyte. Promonocytes have characteristics of both monoblasts and mature monocytes, Cytoplasm: Promonocytes have a moderate amount of blue-gray cytoplasm with fine granules and may have cytoplasmic vacuoles. Nucleus: Promonocyte nuclei are irregular, folded, or convoluted, and have less condensed chromatin than mature monocytes. Monocytes are a type of white blood cell that are part of the immune system and play a key role in defending the body against pathogens: Function Monocytes are produced in the bone marrow and enter the bloodstream, where they can travel to tissues like the spleen, liver, lungs, and bone marrow. They are the largest type of white blood cell. Monocytes act as scavenger cells, ingesting bacteria and other particulate matter, and eliminating infected cells. They also help to repair tissue and influence adaptive immune responses. Appearance Monocytes have a large, kidney-shaped nucleus that is usually centrally placed within the cell. The nucleus has a stranded appearance, when stained, is a pale violet color. The cytoplasm is pale greyish-blue, and contains many dust-like granules of reddish-blue.  CLINICAL APPLICATION OF G-CSF G‐CSF is used as a therapeutically and administrated intravenous or subcutaneous that increased neutrophils count. Short‐acting G‐CSF is given daily. A longer‐acting G‐CSF can be given once in 7–14 days. Indications: Post‐chemotherapy/radiotherapy Stem cell transplantation, Myelodysplasia Aplastic anemia, Severe benign neutropenia,