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Granulopoiesis

Updated on April 23, 2016

It occurs in the following stages in the bone marrow:

a)Pluripotential hemopoietic stem cell

b)Myeloblast

c)Promyelocyte

d)Eosinophil

e)Basophil

f)Neutrophil

Pluropotential hemopoietic stem cell

Also hemocytoblasts. These are stem cells that give rise to all the other blood cells through the process hematopoiesis. They are derived from mesoderm and located in the red bone marrow. They give rise to both myeloid and lymphoid lineages of blood cells.

Myeloblast

It is a unipotent stem cell, which will differentiate into one of the effectors of the granulocyte series. Unipotent stem cell; a cell that can differentiate only along one lineage. The stimulation by G-CSF and other cytokines triggers maturation, differentiation, proliferation and cell survival. It is found in the bone marrow. They are the first recognisable cells in granulopoiesis.

Myelocyte

A myelocyte is a young cell of the granulocyte series, occurring normally in bone marrow and can be found in circulating blood when infected. This stage occurs in all granulocytes. It further differentiates through a series of different stages to results into: a)Basophil b)Neutrophil c)Eosinophil Neutrophils are the only leukocytes to be divided into myelocyte, band and PMN stage.

Promyelocyte

This is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. It differentiates into a myelocyte

Neutrophil

It is staged into:

a)Neutrophilic myelocyte- The developing neutrophil can now be differentiated from basophils and eosinophils as neutrophil specific granules are now being formed.

b)Neutrophilic metamyelocyte-At this stage mitosis can no longer occur. The nucleus elongates, becomes heterochromatic and has a kidney like shape. Differentiation is now much clearer from other granulocytes as the specific granules are in a far greater number than the primary granules formed in the promyelocyte stage.

c) Band cell- As the metamyelocyte matures the nucleus becomes more attenuated and the cell is then called a “band” or “stab” form. Nucleus starts to segment.

d) Neutrophil-Mature neutrophil is formed and the nucleus is segmented and has 3 to 5 lobes. This lobular structure of the nucleus gives rise to the name polymorphonuclear neutrophil

Neutrophil Granules

Primary granules. Mostly alpha granules (azurophilic)Contain primary lysosomesMyeloperoxidase (Membrane proteins)Nitric acid synthase, cathepsins,(matrix microbiocidal) Acid-mucopolysaccharide, heparin-binding protein, (Hydrolases),BPI (bactericidal permeability increasing protein)

Secondary granules Beta granules Strong bactericidal enzymes Lactoferrin Lysozyme , gelatinase, histaminase, heparinase, Sialidase Β2-microglobulin , urokinase-type plasminogen

Basophil

Under the stimulation of GM-CSF and IL-3, the CFU-GEMM differentiates into CFU-Ba . It is staged into: a)Myeloblast & Promyelocyte-These stages are common to all granulocytes and no distinction can be made between different cell lines. b)Basophilic myelocyte & metamyelocyte-Specific granules start to appear in the myelocyte stage, and as the cell develops into the metamyelocyte stage, mitosis ceases. c)Basophil-Final nuclear shape is masked by the high density of cytoplasmic granules. ●

Basophil Granules

Protein components Histamine – binds to H1,2,3 receptors Proteoglycans;Heparin – packaging of basic proteins;Chondriotin sulphates – Packaging (into granules); Enzymes Chymase - inactivate bradykinin, activate angiotensin 1; Tryptase – cleaves C3 ;Cathepsin G-like protease inactivates bradykinin Carboxypeptidase

Others Charcot leyden crystal protein - lysophospholipase MBP Sulphatase

Eosinophil

Under the stimulation of GM-CSF, IL-3 and IL-5 the CFU-GEMM differentiates into the CFU-Eo . It is staged as:

a)Myeloblast & Promyelocyte-These stages are common to all granulocytes and no distinction can be made between different cell lines.

b)Eosinophilic myelocyte & metamyelocyte-Specific granules start to appear in the myelocyte stage and once the cell has reached the metamyelocyte stage it cannot undergo further mitosis.

c)Eosinophil-Mature cell has a bilobed nucleus. There are species specific variations in granule size once stained.

Eosinophil Granules

Primary granules Eosinophil peroxidase Mediate damage to microbes Broncho-constriction and tissue damage ;Charcot –Leyden crystal protein Inflammatory response and respiratory disease

Secondary granules (specific) Eosinophil cytotoxic;Pro-inflammatory proteins eg Major Basic Protein (MBP) release of mediators from Baso and Mast Eosinophil cationic protein (ECP) Eosinophil Derived Neurotoxin (EDN); Arylsulphatase-B

Summary

Neutrophils and monocytes (which evolve into macrophages when they enter the tissues), arise form a common committed progenitor. The myeloblast is the earliest recognizable precursor in the granulocytic series that is found in the bone marrow. On division the myeloblast gives rise to promyelocyte which contain Hematology abundant dark “azurophilic” primary granules that overlie both nucleus and cytoplasm. With subsequent cell divisions these primary granules become progressively diluted by the secondary, less conspicuous “neutrophilic” granules that are characteristic of the mature cells. This concomitant cell division and maturation sequence continues form promyelocytes to early myelocytes, late myelocytes, and they metamyelocytes, which are no longer capable of cell division.As the metamyelocyte matures the nucleus becomes more attenuated and the cell is then called a “band” or “stab” form. Subsequent segmentation of the nucleus gives rise to the mature neutrophil or polymorphonuclear leukocyte. The average interval from the initiation of granulopoiesis to the entry of the mature neutrophil into the circulation is 10 to 13 days. The mature neutrophilic remains in the circulation for only about 10 to 14 hours before entering the tissue, where it soon dies after performing its phagocytic function.

Hematopoiesis
Hematopoiesis

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