MONOCYTOPOIESIS: STAGES, CELL CHARACTERISTICS, REGULATION - BIOLOGY - 2025

The monocytopoiesis is the formation of monocyte-macrophage series the, ie comprises forming monocyte macrophage until activation ends where maturation. Both types of cells fulfill specific functions. Monocytes engulf bacteria and viruses.

For their part, macrophages have high phagocytic activity, attract cells of the immune system and function as antigen presenting cells. They also synthesize important cytokines that participate in the activation of other cell lines.

Left: Monocyte in peripheral blood smear. Right: Macrophage phagocytosing a capsulated yeast (Cryptococcus neoformans). Source: Wikipedia.com/ Carolina Coelho

Monocytes and macrophages as well as other types of cells make up the mononuclear phagocytic system or formerly known as the reticulum endothelial system.

Monocytopoiesis is also called monopoiesis. The monopoietic line is part of the macro process called hematopoiesis, since monocytes are cells that circulate in the blood.

However, monocytes when activated are transported to various tissues. These cells transformed into macrophages will receive a specific name according to the tissue in which they are found.

For example, they are called alveolar macrophages in lung tissue, Kupffer cells in liver, histiocytes in connective tissue, Langerhans cells in skin, microglia in CNS, mesangial cells in kidney, and osteoclasts in bone.

The complete process of monocytopoiesis begins from the Stem Cell. From here the first cells with multipotential functions emerge and then little by little they differentiate into cells committed to the formation of a specific cell lineage.

This happens thanks to chemical factors that regulate the entire process. Among the substances involved are interleukin 3 (IL-3) and granulo-monocytic (GM-CSF) and monocytic (M-CSF) colony-stimulating factors.

A disorder in the monocytopoiesis process can lead to serious diseases.

Stages of monocytopoiesis

The process of formation, differentiation and maturation occurs in the bone marrow. Later the activation process occurs in the tissues of the reticulum endothelial system.

All hematopoietic cell series come from the Stem Cell and monocytopoiesis is no exception. Due to certain chemical stimuli, the Stem Cell will give rise to various multipotential cells.

The first one is the CFU-LM (colony-forming unit of the lymphoid and myeloid series), which later differs into CFU-GEMM (colony-forming unit of the granulocytic, erythrocytic, monocytic and megakaryocytic series). From there it gives rise to CFU-GM (granulocytic and monocytic) and this differs from CFU-M (monocytic).

From here, the recognizable precursors at the bone marrow level begin. These are: monoblast, promonocyte, and monocyte. Then this cell goes out into the peripheral circulation and when activated it becomes a macrophage.

In the process of differentiation from the stem cell to the CFU-M, it is not possible to recognize multipotential precursor cells from a morphological point of view.

Later, during the maturation process of cells from the monoblast to the monocyte or macrophage they undergo sequential morphological changes that reveal their current state of maturation.

That is why, starting from the monoblast, each precursor cell has its own characteristics that make them recognizable.

Characteristics of recognizable stem cells

Monoblast

It is a cell that measures between 15-22 µm. Its characteristics are very similar to the myeloblast, so it is sometimes difficult to differentiate one from the other. It has a nucleus that covers almost the entire cell, leaving a poor cytoplasm that is characterized by being intensely basophilic.

The nucleus is round, eccentric and has a very lax chromatin where 5 to 6 nucleoli are appreciated. Cytochemical staining techniques such as esterase staining can be used to differentiate monoblast from myeloblast.

Its maturation gives way to the promonocyte.

Promonocyte

This cell measures approximately 15-20 µm. The nucleus cytoplasm ratio, although still high, is somewhat lower than that found in the monoblast.

The nucleus remains eccentric but has now assumed an irregular shape and even a slightly kidney-shaped or invaginate area can be seen. The chromatin is slightly condensed and only 1 to 2 nucleoli can be seen.

Cytoplasmic basophilia may be maintained or slightly diminished. At this stage, small azurophilic granules appear. This cell is often confused with the promyelocytes with which it shares some characteristics. As this cell matures, it becomes a monocyte.

Monocyte

Once formed in bone marrow, it remains there for 24 hours and then it is ready to be released into circulation. This cell is easily recognizable in peripheral blood smears.

The monocyte is the largest cell in circulation, measuring between 15-30 µm. It is also the only mature cell that maintains a high nucleus cytoplasm ratio. Although the chromatin is denser than that of the promonocyte, it is less pyknotic than that of the lymphocytes.

The nucleus can be located in the center of the cell or remain eccentric. The shape of the nucleus is variable, sometimes it can be completely kidney-shaped and other times more rounded with a small indentation.

The cytoplasm retains a slight basophilia. With conventional staining, the cytoplasm is observed with a pale blue-grayish hue. The presence of azurophilic granules is maintained throughout the cytoplasm and they are a little more concentrated around the nucleus.

In the cytoplasm of monocytes, the presence of vacuoles may appear, which can be seen under the microscope as white areas. Vacuoles appear in bacterial and viral infectious processes and are due to phagocytic function.

Monocytes and vacuolated macrophages are known as foam cells. They are very common in patients with acquired immunodeficiency. Foam cells are also abundant in atherosclerotic plaques.

In inflammatory processes, monocytes stick to the endothelium thanks to the integrins that they express in their membrane and then cross the vascular endothelium through a process called extravasation. In this way they migrate to various tissues. There they become specialized macrophages depending on the tissue.

Macrophage

It is a large cell, measuring between 25 and 50 µm. It has a well developed oval and central nucleus. The cytoplasm is rich in lysosomes, organelles used in phagocytosis. It is located in various fabrics and each one will receive a different name.

Monocytes and macrophages, together with other cells such as fibroblasts, endothelial and reticular cells, make up the reticulum endothelial system.

Its functions include phagocytizing foreign bodies, presenting processed antigens to other cells of the immune system, synthesizing chemokines that attract other inflammatory cells, regulating cell proliferation and the functioning of the immune response in general.

Regulation of monocytopoiesis

In this process of cell formation, differentiation and maturation, some chemical substances that regulate homeostasis are involved.

These substances include: interleukin 3 (IL-3) and granule-monocytic (GM-CSF) and monocytic (M-CSF) colony-stimulating factors.

Interleukin 3 (IL-3)

It is produced by CD4 lymphocytes. This interleukin favors the differentiation of the Stem-Cell into multipotential precursor cells of all cell lineages, among which is the precursor called the colony-forming unit of the lymphoid and myeloid series (CFU-LM).

Granule-monocytic colony stimulating factor (GM-CSF)

It is a substance that stimulates the bone marrow in the differentiation and maturation processes of various cell lines, including the monocytic line.

Its function is of vital importance to maintain homeostasis in hematopoietic processes. It is also important for the maintenance of the immune response.

This factor is used as therapy in bone marrow transplant patients. This factor helps in the stimulation of the bone marrow and thus quickly recover the number of blood cells.

Monocytic colony stimulating factor (M-CSF)

This substance is synthesized by cells of the medullary stroma and by osteoblasts.

In addition to participating in the process of differentiation of monocyte precursors, it also plays a role in the primary phase of osteoclastogenesis, specifically in the formation of multinucleated giant cells.

It also plays a role in the regulation of lipoprotein levels in the blood. Monocytes are involved in this process. That is why foam cells are formed.

Diseases related to alteration in monocytes

Myocardial infarction

A significant increase in blood monocytes (monocytosis) has been observed in patients who have suffered a myocardial infarction. They are believed to play a critical role in tissue repair.

Atherosclerosis

This involvement is a type of inflammation that occurs at the level of the vascular endothelium. It is stimulated by the increase of lipids in the blood such as cholesterol and low-density lipoproteins (LDL).

Monocytes express receptors with affinity for certain modified lipoproteins, actively acting in atherosclerotic processes. In this sense, interferon alpha (IFNα) stimulates the expression of these receptors on monocytes.

In this condition, it is common to observe an increase in vacuolated monocytes or foam cells in the endothelium.

MonoMAC syndrome

This rare syndrome is characterized by a genetic defect that produces a total absence of monocytes. The bone marrow is unable to produce this cell lineage and as a consequence, recurrent skin infections by opportunistic microorganisms occur.

Sarcoidosis

This is a disease that has a predisposition to form granulomas in various tissues such as lungs, skin, lymph nodes, heart, among others. This disease is caused by the accumulation of inflammatory cells, including the macrophage.

Pulmonary Langerhans cell histiocytosis

This rare disease mainly affects white smokers and is characterized by a proliferation of a specific type of macrophage called Langerhans cells. These are the macrophages normally found on the skin.

In this disease there is an infiltration of these cells in the lung tissue. This situation is believed to be caused by cytokines secreted by alveolar macrophages, especially in smokers. Other tissues such as skin, bone, among others, can also be affected.

Chronic myelomonocytic leukemia (CMML)

It is a myelodysplastic and myeloproliferative neoplastic pathology. It occurs with a significant increase in the number of blood monocytes and with normal leukocytes or slight leukopenia. There may also be thrombocytopenia and normocytic anemia.

Macrophage activation syndrome (SAM)

This disease is characterized by a proliferative and functional macrophage abnormality. Its morphology is normal but its activity is exaggerated. Macrophages begin to engulf erythrocytes, platelets, leukocytes, and even their own precursors in an uncontrolled manner. The disease can be fatal if it is not treated in time.

References

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