Megakaryocyte

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Megakaryocytes
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Megakaryocyte
Two megakaryocytes in bone marrow, marked with arrows.
Details
LocationBone marrow
FunctionPlatelet production
Identifiers
Latinmegakaryocytus
MeSHD008533
THH2.00.04.3.05003
FMA83555
Anatomical terms of microanatomy

A megakaryocyte (

clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases.[1] Owing to variations in combining forms
and spelling, synonyms include megalokaryocyte and megacaryocyte.

Structure

In general, megakaryocytes are 10 to 15 times larger than a typical red blood cell, averaging 50–100 μm in diameter. During its maturation, the megakaryocyte grows in size and replicates its DNA without cytokinesis in a process called endomitosis. As a result, the nucleus of the megakaryocyte can become very large and lobulated, which, under a light microscope, can give the false impression that there are several nuclei. In some cases, the nucleus may contain up to 64N DNA, or 32 copies of the normal complement of DNA in a human cell.

The cytoplasm, just as the platelets that bud off from it, contains α-granules and dense bodies.

Development

Blood cell lineage
Blood cell lineage

Megakaryocytes are derived from

The megakaryocyte develops through the following lineage:

CFU-Me (

→ megakaryocyte.

The cell eventually reaches megakaryocyte stage and loses its ability to divide. However, it is still able to replicate its DNA and continue development, becoming

polyploid.[4] The cytoplasm continues to expand and the DNA amount can increase up to 64n in humans and 256n in mice. Many of the morphological features of megakaryocyte differentiation can be recapitulated in non-hematopoietic cells by the expression of Class VI β-tubulin (β6) and they provide a mechanistic basis for understanding these changes.[5]

Function

Platelet release

Once the cell has completed differentiation and become a mature megakaryocyte, it begins the process of producing platelets. The maturation process occurs via endomitotic synchronous replication whereby the cytoplasmic volume enlarges as the number of chromosomes multiplies without cellular division. The cell ceases its growth at 4N, 8N or 16N, becomes granular, and begins to produce platelets.[6] Thrombopoietin plays a role in inducing the megakaryocyte to form small proto-platelet processes. Platelets are held within these internal membranes within the cytoplasm of megakaryocytes. There are two proposed mechanisms for platelet release. In one scenario, these proto-platelet processes break up explosively to become platelets.[7] It is possible to visualize the spontaneous release of platelets using holotomographic live-cell imaging. Alternatively, the cell may form platelet ribbons into blood vessels. The ribbons are formed via pseudopodia and they are able to continuously emit platelets into circulation. In either scenario, each of these proto-platelet processes can give rise to 2000–5000 new platelets upon breakup. Overall, 2/3 of these newly produced platelets will remain in circulation while 1/3 will be sequestered by the spleen.[medical citation needed]

Example of platelets release in mature megakaryocytes. This footage shows the formation and spontaneous release of platelets (small round-shaped blood cells), imaged with a live-cell imaging microscope.

Thrombopoietin (TPO) is a 353-amino acid protein encoded on chromosome 3p27. TPO is primarily synthesized in the liver[8] but can be made by kidneys, testes, brain, and even bone marrow stromal cells. It has high homology with erythropoietin. It is essential for the formation of an adequate quantity of platelets.

After budding off platelets, what remains is mainly the cell nucleus. This crosses the

bone marrow barrier to the blood and is consumed in the lung by alveolar macrophages
.

Effects of cytokines

PF4, CXCL5, CXCL7, and CCL5 inhibit platelet formation.[10]

Clinical significance

Megakaryocytes are directly responsible for producing platelets, which are needed for the formation of a thrombus, or blood clot. There are several diseases that are directly attributable to abnormal megakaryocyte function or abnormal platelet function.[11]

Essential thrombocythemia

hydroxyurea
to lower platelet levels.

Congenital amegakaryocytic thrombocytopenia

bone marrow transplantation
.

Bone marrow/stem cell transplant is the only remedy for this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death until transplant has been completed, although this is not always the case.

There appears to be no generic resource for CAMT patients on the web and this is potentially due to the rarity of the disease.

History

In 1906, James Homer Wright provided evidence that megakaryocytes give rise to blood platelets.[17]

Kelemen first coined the term "thrombopoietin" to describe the humoral substance responsible for the production of platelets.[18]

See also

References

External links