MAST CELLS: ORIGIN AND FORMATION, CHARACTERISTICS AND FUNCTIONS - BIOLOGY - 2024

The mast cells are leukocytes derived from hematopoietic stem cells from bone marrow to complete their maturation in the tissue. They are present in practically all groups of vertebrates; in humans, they have a rounded shape, with a diameter of 8-20 micrometers.

These cells do not circulate freely in the bloodstream but are ubiquitous in connective tissues, mainly in association with blood vessels. They are similar in composition to basophilic granulocytes and can degranulate in response to similar stimuli.

Mast cell or Mast Cell (in English). Taken and edited from: Dr. Roshan Nasimudeen.

Mast cells have numerous functions, among which are phagocytosis and antigen processing, as well as the release of cytokines and substances with activity on blood vessels, but they must be activated in order to exercise their function.

They contain heparin, a powerful blood anticoagulant, as well as histamine that causes dilation of blood capillaries and increases capillary permeability, for which they are related to inflammatory and immunological mechanisms.

The increase in the number of mast cells can trigger a disease called mastocytosis. Symptoms of the disease include pruritus, cardiac arrhythmia, decompensation, dizziness, dyspnea, diarrhea, nausea and headaches, among others.

Origin and formation

Mast cells are derived from a pluripotential hematopoietic cell located in the bone marrow. After their formation, they will migrate as immature and undifferentiated agranular cells, called CD34 + precursor cells, to the connective tissues via the bloodstream.

Once in the connective tissue, mast cells mature and perform their functions. However, not all the precursor cells that reach the connective tissue will mature and differentiate, but some will remain undifferentiated, acting as reserve cells.

During their maturation, mast cells will form secretory granules and express different receptors on their surface. Several cytokines and other compounds participate in the growth and differentiation process of mast cells.

A very important cytokine in this process is called the stem cell factor (CSF). This factor will be in charge of inducing the development, differentiation and maturation of mast cells from their parents; with the help of a transmembrane receptor of the tyrosinkinase type called KIT.

The ability to stay, move and interact with the extracellular matrix of the different tissues is due in part to their ability to adhere through the integrins to various proteins located in the extracellular matrix, including laminins, fibronectins and vitronectins.

characteristics

Mast cells are rounded or ovoid cells with a diameter of 8-20 micrometers, with folds or microvilli on their surface. Its core is rounded and is located in a central position.

The cytoplasm is abundant, the mitochondria few, with a short endosplamatic reticulum and numerous free ribosomes. Numerous secretory granules having a diameter of approximately 1.5 µm are also present in the cytoplasm. They are surrounded by a membrane and their content varies depending on the species.

These granules are metachromatic, that is, during staining they acquire a color different from that of the dye with which they are dyed. Additionally, they present lipid bodies in the cytoplasm, which are structures not surrounded by membranes that serve for the storage of arachidonic acid.

A fundamental characteristic of mast cells is that they always leave the bone marrow without being matured, unlike basophils and other blood cells.

Types

Within the same organism, mast cells make up a heterogeneous group of cells that, in rodents, can be distinguished into two large groups, based on their morphological, functional and histochemical characteristics.

Mast cells of connective tissues

Located in the connective tissue of the skin, mainly surrounding the blood vessels and the peritoneum. They have granules that react with safranin (vital dye), acquiring a red color.

These mast cells have a large amount of histamine and heparin and participate in the defense against bacteria. They also express the enzymes called Rat Mast Cell Protease I (CTMC-I), which is equivalent to chymase in humans and CTMC-VI and VII, equivalent to tryptase, as well as heparin.

Mucosal mast cells

They are found mainly in the intestinal mucosa and respiratory tract. These mast cells are dependent on cytokines derived from T lymphocytes. Their histamine content is lower than that of mast cells in connective tissues.

These mast cells express the enzyme called RMCP-II, which is equivalent to chymase in humans, as well as chondroitin sulfate.

Cytology of a tumor. The cells seen are mast cells. Taken and edited from: Joel Mills.

In humans

In humans, mast cells also differ into two subtypes, which are equivalent to those in rodents. But among the differences that exist between both groups of organisms is the fact that both types of mast cells, in humans, can coexist in different types of tissues.

Human MC _TC mast cells are equivalent to rat connective tissue mast cells. These express tryptase, chymase and also carboxypeptidase, and are more abundant in the skin and intestinal submucosa.

Human MC _T mast cells, for their part, are equivalent to mucosal mast cells. The only neutral protein that they express is tryptase and they are more frequent in the intestinal mucosa.

Features

These cells have multiple functions that they exert by releasing multifunctional biochemical messengers, which are contained within the granules.

Innate immunity

Mast cells located in the connective tissue of the skin act as watchdogs, defending the body from bacteria and other pathogens. These cells have a wide variety of receptors on their surface, which can interact with microorganisms and activate the defensive response.

Acquired immunity

Mast cells have the ability to phagocytose, process, and capture antigens, but they can also modulate growth and promote lymphocyte recruitment. They are also capable of activating macrophages and lymphocytes through the secretion of cytokines and chemokines.

Allergies

There are several types of cells that participate in the body's allergic response mechanisms. Mast cells participate as initial effectors by recognizing the causative agent of the allergy through the Fc-IR receptors and releasing the contents of their granules.

The granules contain numerous substances including primary and secondary mediators and enzymes. These mediators include, for example, heparin, histamine (primary), prostaglandins, leukotrienes and interleukins (secondary).

The release of the mediators produces various effects such as favoring pro-inflammatory mechanisms, activating platelets, eosinophils and neutrophils, increasing the permeability of the vascular walls and inducing muscle contraction in the airways.

Allergic reactions can have local effects, for example on rhinitis (nasal mucosa), or they can be general, in which case anaphylactic shock occurs.

Repair of damaged tissues

Tissue repair is one of the processes in which mast cells participate. This process should lead to the restoration of normal tissue structure and function after damage. However, sometimes the repair may be impaired resulting in tissue fibrosis.

For example, tissue fibrosis of the basement membrane of the respiratory epithelium during allergic asthma seems to be related to repeated mast cell stimulation. On the other hand, during wound repair, mast cells promote fibroblast migration and formation.

Bone marrow mast cells, observed using the Wright staining method. Taken and edited from: Ed Uthman of Houston, TX, USA.

Angiogenesis

Different cells are involved in the formation of new blood vessels, as well as in the migration, proliferation, formation and also in the survival of endothelial cells through the production of angiogenic growth factors.

Cells that promote angiogenesis include fibroblasts, T lymphocytes, plasma cells, neutrophils, eosinophils, as well as mast cells.

Regulation of tissue function

In the intestinal epithelium, mast cells regulate activities such as water and electrolyte secretion, blood flow, vessel constriction, endothelial permeability, intestinal motility, pain perception, cell flow in the tissue, as well as the cellular activity of neutrophils, eosinophils and lymphocytes..

Mast cell degranulation

During the response of mast cells to inflammatory processes, they release the content of their granules in a mechanism that is called degranulation. There are two types of degranulation:

Explosive degranulation

Also called anaphylactic degranulation or mixed exocytosis. In this case, the granules swell and become less dense, with a fusion of the granule membranes with each other and with the plasma membrane. In addition, the formation of secretion channels is created that communicate with the granules located deeper in the cytoplasm.

In this way, a massive and punctual secretion of the content of the granules to the outside of the cell will occur. It occurs during allergic responses.

Slow degranulation

In this case there is no fusion of membranes, but the amounts of granular content released will be lower and will occur in longer periods of time. They occur in tissues with chronic or tumorous inflammations.

Normal values

Mature mast cells are not found free in the bloodstream, but in connective tissues and other types of tissues. There are no reference values ​​for these cells.

However, densities of 500 to 4000 cells / mm ³ are considered normal values in the lungs, while in the skin their values ​​range between 700 and 1200 cells / mm ³ and close to 20,000 in the epithelium of the gastrointestinal tract.

Systemic mastocytosis

Systemic mastocytosis (MS) is a clonal disease of the mast cell progenitors of the bone marrow that causes a proliferation of the number of mast cells to levels above normal.

The disease can present in an asymptomatic or indolent form, however, it can also manifest itself in a highly aggressive form, in which case the mortality levels are very high (mast cell leukemia).

Mastocytosis can occur at any age, but they have a higher incidence in adults. Symptoms of the disease are related to the products secreted by mast cells and include vascular instability or anaphylactic shock with no apparent cause, redness of the skin, diarrhea or headaches, among others.

To date, there is no effective treatment to cure mastocytosis, although there are treatments to control it in patients with severe bone lesions, severe mastocytosis, or intestinal conditions. These treatments range from prednisolone to chemotherapy.

References

1. PR Weather, HG Burkitt & VG Daniels (1987). Functional Histology. 2nd edition. Churchill Linvingstone.
2. Mast cell. On Wikipedia. Recovered from en.wikipedia.org.
3. MJ Molina-Garrido, A. Mora, C. Guillén-Ponce, M. Guirado, MJ Molina, MA Molina & A. Carrato (2008). Systemic mastocytosis. Systematic review. Annals of Internal Medicine.
4. DD Metcalfe, D. Baram & YA Mekori. 1997. Mast cells. Physiological reviews.
5. Cell Types: Mast cells. Atlas of Plant and Animal Anatomy. Recovered from mmegias.webs.uvigo.es.
6. Mast cells. Recovered from ecured.cu.