MONOCYTES: CHARACTERISTICS, FUNCTIONS, VALUES, DISEASES - BIOLOGY

The monocytes are blood cells that belong to a leukocyte subpopulation called mononuclear phagocyte system. They have a common origin with other phagocytes in hematopoietic stem cells. They are responsible for the regulation of innate and adaptive immunity, as well as tissue remodeling and homeostasis.

There are two subgroups of monocytes that differ in their functions and destinations, namely: 1) one that produces macrophages after extravasation from the peripheral circulation; 2) another that, under inflammatory conditions, differentiates into inflammatory dendritic cells.

Source: Dr Graham Beards

Macrophages are phagocytic cells resident in lymphoid and non-lymphoid tissue. They are involved in steady-state tissue homeostasis by eliminating apoptotic cells. In addition, they possess a wide range of receptors that recognize pathogens.

For their part, dendritic cells specialize in the processing and presentation of antigens, and in controlling the response of B and T cells.

In addition to defending against infections, monocytes can contribute to the appearance of diseases, such as atherosclerosis and multiple sclerosis, or, conversely, they can contribute to muscle regeneration after damage, and to the degradation of amyloid fibrils in Alzheimer's disease.

characteristics

Monocytes are cells of irregular shape. They have a kidney-shaped nucleus. They have vesicles in the cytoplasm. Its diameter ranges from 16 to 24 µm. When monocytes are stained with Wright's stain, their cytoplasm appears bluish in color.

They are derived from pluripotent stem cells from the bone marrow. Monocytes are produced by several intermediate stages and stages including: 1) a common myeloid progenitor (CMP); 2) a granulocyte-macrophage progenitor (GMP); 3) the macrophage-dendritic cell progenitor (MDP).

They have plasticity because they can become macrophages or dendritic cells. They become macrophages when they enter tissues or could differentiate into inflammatory dendritic cells.

In humans, monocytes constitute 8% of leukocytes and have a half-life of 70 hours, while in mice they constitute 4% of leukocytes and have a half-life of 17 hours.

Based on the expression of chemokine receptors, monocytes are divided into two main groups. In humans these are: CD14 ⁺⁺ CD16 ^- and CD14 ⁺ CD16 ⁺. In the mouse these are Gr-1 ^hi and Gr-1l ^ow.

Monocyte development is determined by the expression of specific transcription factors, such as PU.1, and the displacement factors CCAAT, AML-1B, Sp-1, GATA-1, and -2.

Origin and development

Current mouse-based models propose that monocytes originate in the bone marrow from haematopoietic stem cells (HSC), which evolve towards the formation of a granulocyte-macrophage (GMP) progenitor, which is forms a macrophage-dendritic cell progenitor (MDP) and a common monocyte progenitor (cMoP).

In the lumen of blood vessels, at steady state, cMoP differentiates first into LY6C ^hi cells, and then into LY6C ^low cells. Mouse LY6C ^low cells (their human equivalent is CD14 ^low CD16 ⁺), become blood-resident macrophages rather than monocytes themselves, and move on the surface of the endothelial lumen.

LY6C ^low cells coordinate the stress response in the lumen, and respond, via the 7 Toll-like receptor, to signals of local damage, inducing the recruitment of neutrophils. This triggers necrosis of the endothelium and, consequently, LY6C ^low monocytes clean the cell debris.

Mouse LY6C ^hi cells (their human equivalent is CD14 ⁺) represent the "classical monocytes." They are recruited at sites of inflammation that act as precursors to peripheral mononuclear phagocytes. LY6C ^hi cells play an important role in the host's response to attack by pathogens, such as Listeria monocytogenes.

Monocyte-derived macrophages

The term macrophage refers to large phagocytic monumental cells. Depending on the tissue in which they are found, macrophages are given specific names.

Macrophages are called Kupffer cells in the liver, alveolar macrophages in the lungs, histiocytes in connective tissue, osteoclasts in bone, microglia in the brain, and Langerhans cells in the skin. They are also named after the organ where it is found, such as lymph node, thymus, or endocrine macrophages.

Under steady-state conditions, the tissue-resident macrophage populations are maintained by their local proliferation. However, when there is inflammation a rapid recruitment of precursor cells takes place into the macrophage compartment of the respective tissue.

The differentiation of LY6C ^low monocytes to macrophage involves changes in the expression of genes, which determine the phenotypic changes and the expression of surface antigens associated with the macrophage. There are two types of macrophages, namely: M1 macrophages or inflammatory macrophages; M2 macrophages or anti-inflammatory (or regulatory) macrophages.

M1 macrophages react strongly to invasion by pathogens and other harmful signals through the formation of proinflammatory cytokines, and the synthesis of nitric oxide and reactive oxygen species. M2 macrophages have tolerogenic and restorative properties.

Monocyte-derived dendritic cells

Classic dendritic cells develop from a macrophage-dendritic cell (MDP) progenitor, termed a preclassical dendritic cell. Dendritic cells are formed from monocytes that migrate through the endothelium in the ablumenal – lumenal direction. Monocytes in the endothelial matrix develop into macrophages.

Recruitment of LY6C ^hi cells occurs at the site of inflammation. The recruited LY6C ^hi cells transform into dendritic cells, which migrate to the lymph nodes. The LY6C ^hi monocytes are converted into CX ₃ CR1 ⁺ D14 ⁺ dendritic cells. Preclassic dendritic cells convert to CD103 ⁺.

When inflammation occurs in the skin by irradiation with UV light, the monocytes LY6C ^hi enter the epidermis and become cells with characteristics of Langerhans cells. These cells are also usually found in the mucous epithelial line of the vaginal and oral cavities.

The dendritic cells of the vaginal epithelium are reconstituted by precursor cells of the bone marrow. Under inflammatory conditions they are repopulated by monocytes LY6C ^hi.

Features

Role of monocytes in infection

In healthy individuals, monocytes in peripheral blood consist of 90% classical monocytes (CD14 ⁺⁺ CD16 ⁺⁺). The remaining 10% are CD16 ⁺ monocytes (CD14 ⁺⁺ CD16 ⁺ intermediates) and non-classical monocytes (CD14 ⁺ CD16 ⁺).

During any infection or injury, neutrophils respond quickly (within hours). However, monocytes modulate inflammation through the production of cytokines, such as IL-1β, IL-6, TNF-α, and inducible nitric oxide synthase. Each type of monocyte responds differently to stimuli.

For example, during infection with Candida albicans, classical monocytes induce the Th7 immune response. Whereas in infection with Aspergillus fumigatus, classical monocytes and CD16 ⁺ have similar phagocytosis capacities, and classical monocytes inhibit conidia germination.

Under infection conditions, the number of CD16 ⁺ monocytes increases. This has been observed in pregnant women with malaria (Plasmodium spp.) And coinfected with HIV. Monocytes can reduce the number of parasites, phagocytizing infected erythrocytes via opsonic or non-opsonic phagocytosis.

However, monocytes can contribute to the severe manifestations of malaria, which affects the physiological functions of the host and leads to the appearance of pathologies. Monocytes, dendritic cells, and macrophages also play a critical role in the pathogenesis of HIV.

Role of monocytes in angiogenesis and atherogenesis

Monocytes accumulate in the wall of growing vessels, suggesting that they contribute to atherogenesis. They do not form vascular networks, but they mimic endothelial cells, with which they share phenotypic characteristics and surface markers.

When monocytes in the peripheral circulation migrate from the vascular to the extravascular compartment, they mature into macrophages. Specifically, M2 macrophages possess proangiogenic functions: they promote vascular remodeling during tissue repair.

A characteristic of the formation of atherosclerotic plaque is the accumulation of lipoproteins in the intima region of the artery, which is accompanied by the recruitment of monocytes from the circulation.

Monocytes migrate to the subendothelial space and interact with components of the extracellular matrix, such as collagen I, the main constituent of the wall of the arteries. A strong interaction is established between the extracellular matrix and monocytes.

Low-density lipoproteins (LDL), retained by proteoglycans in the extracellular matrix, are captured by macrophages. Matrix metalloproteinases (MMPs) are important for atheroclerotic plaque formation. Macrophages are responsible for producing urokinase that activates MMPs.

Role of monocytes in inflammation

Monocyte subsets markers of many inflammatory conditions, such as acute myocardial infarction, stroke, sepsis, rheumatoid arthritis, HIV, and hemodialysis. For example, patients with myocardial infarction and ventricular aneurysm have many more monocytes than individuals without these pathologies.

Monocytes and macrophages are the main source of cytokines, which serve as intercellular messengers, and regulate cell proliferation, differentiation, and migration. The most important cytokines involved in heart failure are tumor necrosis factor (TNF) and interleukin IL6.

A study of inflammatory processes in patients with heart failure showed that TNF, TNFR1 and TNFR2 are predictors of mortality in the population studied. IL6 is not a marker of inflammation, but has a direct deleterious effect on the myocardium.

Therapeutic modulation of the cytokine system in clinical trials has not been successful in humans. Another strategy is the use of carvedilol, a non-selective beta-adrenoreceptor antagonist, which reduces the production of TNF by monocytes.

Fenofibrate, a derivative of fibric acid, significantly inhibits the release of monocyte-derived cytokines, such as IL1, IL6, and MCP-1.

Monocyte levels in the blood

Quantitative analysis of the different types of leukocytes in the blood indicates the following normal values: band shapes (neutrophilic granulocytes), 3–5%; segmented (neutrophilic granulocytes), 40–75%; eosinophils (granulocytes), 2–4%; basophils (granulocytes), 0–1%; lymphocytes, 25–40%; monocytes, 2–8%.

The normal number of monocytes in the blood is between 0 and 800 cells / µl, and the normal average value is 300 cells / µl (0.3 x 10 ⁹ cells / L). Chronic inflammatory processes are associated with monocytosis, which is an increase in the number of monocytes. The absolute value exceeds 800 cells / µl (> 0.8 x 10 ⁹ cells / L).

Some disorders associated with monocytosis are inflammatory diseases, such as tuberculosis, syphilis and subcutaneous bacterial endocarditis, granulomatosis / autoimmune, systemic lupus erimatous, rheumatoid arthritis, and temporal arteritis.

Malignant disorders that cause monocytosis include preleukemia, nymphocytic leukemia, histiocytosis, Hodgkin's disease, non-Hodgkin's lymphoma, and carcinomas.

Monocytopenia is a reduction in the number of monocytes (less than 200 cells / µl; 0.2 x 10 ⁹ cells / L). It occurs in response to stress, endotoxemia, and following the administration of glucocorticoids, interferon alpha, and TNF-alpha.

Some disorders associated with monocytopenia are chronic lymphocytic leukemia, cyclic neutropenia, and severe thermal damage.

Related diseases: cancer

Monocytes, in addition to having an important role in the innate immune system to defend the host from pathogenic microbes, also participate in the pathogenesis and progression of diseases such as atherosclerosis, multiple sclerosis, and tumor metastasis.

Inflammatory M1 macrophages are involved in the elimination of unnecessary tumor cells, but M2 tumor associated macrophages (TAMs) can inhibit the antitumor response, increasing tumor growth and promoting metastasis.

Due to this, the presence and quantity of TAM is correlated with a poor life expectancy for the patient. In mice in which the spleen has been removed, they show a reduction in the number of TAMs, which is why reduced tumor growth and metastasis are observed.

Within the hypoxic environment of the tumor, TAM is strongly influenced by the secretion of signal molecules, cells of the immune system, and tumor cells. Invasive TAMs produce growth factors such as EGF, which promote tumor growth.

Additionally, TAM produces factors like VEGF, which promote blood vessel growth and metastasis. Another factor produced by TAM is VEGFR1, which is involved in the formation of a premetastatic niche.

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MONOCYTES: CHARACTERISTICS, FUNCTIONS, VALUES, DISEASES - BIOLOGY - 2025