- Mastocytes - occurrence
- Mastocytes - degranulation
- Mast cells - types
- Mastocytes - allergic reactions
- Mast cells - role in the body
- Mastocytes - mastocytosis
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Mast cells are cells that, until recently, were thought to be involved only in the pathomechanism of allergic reactions. However, recent years of research have proved that they are also crucial in a number of innate and acquired immune responses. Mast cells can be involved in the process of cancer formation, defense against microbes, the development of autoimmune diseases, and perhaps even diseases related to the nervous system.
Contents:
- Mastocytes - occurrence
- Mastocytes - degranulation
- Mast cells - types
- Mastocytes - allergic reactions
- Mast cells - role in the body
- Mastocytes - mastocytosis
Mast cells , ormast cells , are cells of the immune system 6-12 mm in size. They were first described by Paul Ehrlich in 1876. A characteristic feature of mast cells is the presence of 50-200 basophil granules in their cytoplasm containing bioactive substances, e.g. histamine.
Immature mast cells that do not yet contain granules are released from the bone marrow into the peripheral blood. Only when the mast cell settles in the target tissue, under the influence of growth factors, matures and forms granules.
This is quite unusual, as most blood cells are not released into the peripheral blood until they reach maturity in the marrow.
The lifetime of mast cells in tissues ranges from several weeks to several months. After this time, the mast cell nucleus is fragmented and the mast cell itself completes the life cycle in the spleen.
Mastocytes - occurrence
Mast cells are found in many tissues, mainly in places of potential contact with harmful substances, such as the skin, mucosa of the respiratory tract, gastrointestinal tract and the genitourinary system.
In addition, mast cells fill connective tissue, especially in the areas surrounding blood vessels, nerve cells, smooth muscle cells, mucous glands, and hair follicles.
Mastocytes - degranulation
Mast cells are characterized by the content of basophilic granules in their cytoplasm containing various bioactive substances:
- biogenic amines(histamine, serotonin)
- cytokines (IL-1, IL-3, IL-4, IL-5, IL-6, IL-8 IL6, INF-gamma, TNF-alpha, TGF-beta)
- enzymes (chymase, tryptase, hydrolases, phospholipases, granzymes B and H, cathepsin G)
- lipid metabolites (leukotrienes, prostaglandins, PAF)
- adenosine triphosphate (ATP)
- Vasoactive intestinal peptide (VIP)
- nitric oxide (NO)
- heparin
- endothelial growth factor (VEGF)
- proteoglycans
It is important to note that mast cells are a very heterogeneous group of cells, and no single cell produces all of these substances simultaneously.
Bioactive substances from the granularity are released through the degranulation process that occurs under the influence of:
- type I allergic reaction e.g. after contact with grass pollen
- drugs, e.g. quinine, morphine, non-steroidal anti-inflammatory drugs
- physical factors, e.g. heat, cold, vibration, pressure, exercise
- chemical agents, e.g. alcohol, insect venoms
- strong stress
- procedures, e.g. endoscopy, biopsy
Mast cells - types
There are two types of mast cells in the human body, and the division criterion is the grain content:
- mucosal mast cells( T mast cells ) tryptase-containing mainly in the mucosa
- connective tissue mast cells( TC mast cells ) containing tryptase and chymase found in connective tissue
Mastocytes - allergic reactions
Mast cells play a central role in Type I allergic reactions. This reaction is stimulated by specific allergen-bound IgE antibodies which, when combined with a mast cell receptor (FcεRI), initiate immediate cell degranulation.
The release of histamine, leuktrienes, serotonin, prostaglandins and other substances that act locally (causing e.g. swelling of the nasal mucosa) or systemically (causing e.g. chronic fatigue).
These reactions are immediate, which means that there are seconds-minutes from contact with the allergen.
Skin tests commonly used in the diagnosis of allergic diseases detect the presence of mast cells "allergic" to a given allergen.
Mast cells - role in the body
Until recently, mast cells were thought to be just cells in type I allergic reactions. However, it turns out that their role in the body is much broader and includes various responses to innate and acquired immune responses.
They have been shown to play a role in the immune response against microorganisms to which mast cells react, similarly to allergic reactions, by releasing histamine and increasing the permeability of blood vessels. This makes it easier for other cells of the immune system, e.g. neutrophils, to access the site of infection.
Presence of mast cells in strategic places like:
- respiratory system
- digestive system
- genitourinary tract
- skin
allows them to act as a "guard" and prevent the microorganism from entering the body.
Mast cells on their surface have TLR receptors (Toll-like receptors), which are activated by bacterial and viral antigens.
In addition, their role in the regulation of the inflammatory process is emphasized, where mast cells are the direct initiator of the inflammatory process.
On the other hand, they can also inhibit the inflammatory process by secreting substances such as IL-10 or TGF-β.
In addition, mast cells can reduce the activity of macrophages and dendritic cells and are involved in all stages of tissue repair during and after an inflammatory reaction.
Another important function of mast cells is their close cooperation with T lymphocytes, which influence the development of immune tolerance to their own tissues. Particularly important is their influence on regulatory T lymphocytes (Treg), which prevent the development of autoimmune diseases.
The role of mast cells in autoimmune diseases is described, among others, by in systemic lupus erythematosus and rheumatoid arthritis, where it has been shown that mast cells can stimulate autoreactive T cells, thus enhancing tissue damage.
The participation of mast cells in the neoplastic process has also been documented.
First, mast cells may have anti-tumor effects by secreting TNF-alpha, which has a cytotoxic effect on tumor cells.
Secondly, they can also act pro-cancer by stimulating the production of new blood vessels in the tumor (angiogenesis).
Mastocytes - mastocytosis
Mastocytosis is a group of proliferative diseases characterized by excessive division and accumulation in mast cell organs, especially in the bone marrow and skin. It is estimated that mascytosis affects 1 in 1,000-8,000 people. It affects both children and adults.
Most patients with mastocytosis have a mutation in the KIT gene at codon 816 (mutation D816V). The KIT gene codes for a receptor on the surface of mast cells that, when stimulated by growth factors, causes proliferationcells.
The consequence of the D816V mutation is continuous stimulation of the receptor even without connection with a growth factor and uncontrolled mast cell proliferation.
Symptoms of mastocytosis may be systemic in nature, resulting from the release by mast cells of substances contained in granules, such as histamine and pro-inflammatory cytokines. A systemic symptom is e.g. hot flashes.
On the other hand, local symptoms result mainly from the accumulation of mast cells in the tissues, which may cause, for example, swelling and redness of the skin. Other symptoms of mastocytosis are:
- anemia
- enlargement of the spleen and liver
- reddish brown itchy lumps on the skin
- Darier's symptom (appearance of hives or linear blisters due to skin irritation)
- drop in blood pressure
- shock
- headache
- fever
- bone pain
- chronic fatigue
- weight loss
- diarrhea
- stomach ache
- depression
- mood disorders
Mastocytosis is characterized by a wide spectrum of clinical forms:
- cutaneous mastocytosis
- mild systemic mastocytosis
- systemic mastocytosis associated with clonal non-mastocytosis
- aggressive systemic mastocytosis
- mast cell leukemia
- mast cell sarcoma
- subcutaneous mastocytoma
Cutaneous mastocytosis is more common in children and systemic mastocytosis in adults.
Worth knowing…Recently, mast cells have been shown to be involved in the development of chronic fatigue syndrome.
Stimulation of mast cells increases the secretion of pro-inflammatory cytokines, which may result in fatigue, lack of strength and malaise.
Additionally, mast cells can be located within nerve cells, and by producing serotonin, they can directly influence the activity of the nervous system.
There is also strong evidence that mast cells can cross the blood-brain barrier and migrate from the blood directly to the brain.
About the author
Karolina Karabin, MD, PhD, molecular biologist, laboratory diagnostician, Cambridge Diagnostics PolskaA biologist by profession, specializing in microbiology, and a laboratory diagnostician with over 10 years of experience in laboratory work. A graduate of the College of Molecular Medicine and a member of the Polish Society of Human Genetics. Head of research grants at the Laboratory of Molecular Diagnostics at the Department of Hematology, Oncology and Internal Diseases of the Medical University of Warsaw. Doctor of Medical Sciences inin the field of medical biology, she defended at the 1st Faculty of Medicine of the Medical University of Warsaw. Author of many scientific and popular science works in the field of laboratory diagnostics, molecular biology and nutrition. On a daily basis, as a specialist in the field of laboratory diagnostics, he runs the content department at Cambridge Diagnostics Polska and cooperates with a team of nutritionists at the CD Dietary Clinic. He shares his practical knowledge on diagnostics and diet therapy of diseases with specialists at conferences, training sessions, and in magazines and websites. She is particularly interested in the influence of modern lifestyle on molecular processes in the body.
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