Mast Cells: Definition, Origin, Location, Function, Mechanism of Action and Associated Disorders

We are talking about cells belonging to the immune system.

Mast cells were first described by Paul Ehrlich in 1878, since then they have been seen primarily as allergy effectors.

Only in the last two decades have mast cells gained recognition for their participation in other physiological and pathological processes.

With continued research on mast cells, new knowledge is developing and the list of conditions, disorders, and diseases that involve mast cell involvement is growing.

No one has been found with very few or no mast cells, indicating to some scientists that we may not be able to survive with very few mast cells.

Origin of mast cells

Mast cells are derived from the bone marrow, but unlike other white blood cells, mast cells are released into the blood and do not fully mature until they are recruited into tissue where they undergo terminal differentiation.

Stem cell factor is an essential cytokine for mast cell development, proliferation, and survival.

Mast cells can be distinguished from other cell types in tissue sections by staining with toludine blue which stains mast cells blue.

Location

Mast cells are produced in the bone marrow, travel through the circulatory system, and enter all tissues of the body.

Mast cells have a generalized distribution and are found predominantly at the interface between their containing tissue and the environment.

Mast cells are located in connective tissue, including the skin, the linings of the stomach, on the mucosal surfaces of the intestine and lungs, and around blood vessels and other tissues.

Function

Mast cells are tissue resident cells that play an important role in many inflammatory settings.

These actors are key in the inflammatory response, as they can be activated to release a wide variety of inflammatory mediators, by many different antigens, including allergens, pathogens, and physiological mediators.

Mast cells also appear to have this diversity of functions. This is seen when they are detected around wounds, and can play an important role in wound healing.

For example, the typical itch around a healing scab can be caused by histamine released by mast cells.

Researchers also think that mast cells may play a role in the growth of blood vessels (angiogenesis).

Mast cells have traditionally been viewed as effector cells for allergic reactions that can store and re-synthesize many mediators upon activation by a variety of stimuli.

Exciting new insights reveal the role of mast cells in the pathogenesis of connective tissue disorders and fibrosis.

Local therapeutic manipulation of the mast cell population and reactivity can help improve and even prevent impaired repair processes for which there is no cure.

Mast cell maturation, phenotype, and function are a direct consequence of the local microenvironment and have a marked influence on their ability to specifically recognize and respond to various stimuli through the release of a series of biologically active mediators.

These characteristics allow mast cells to act as the first response to harmful situations, as well as to respond to changes in their environment by communicating with a variety of other cells involved in physiological and immune responses.

Therefore, the critical role of mast cells in both innate and adaptive immunity, including immune tolerance, has gained greater prominence.

Conversely, mast cell dysfunction has singled out these cells as the primary aggressors in various chronic allergic, inflammatory, cancer, and autoimmune disorders.

Mechanism of action

Mast cells play an important role in helping to defend these tissues from disease.

Each mast cell possesses storage sacs or secretory granules, which contain powerful biologically active molecules called mediators.

Triggers include a variety of different foods, exercises, chemicals, fragrances, and stress.

By releasing chemical “alarms” such as histamine, mast cells attract other key players of the immune defense system to areas of the body where they are needed

Mast cell disorders

There are two main forms of mast cell disorders: mastocytosis, where the body produces too many mast cells, and Mast Cell Activation Syndrome, where even the normal number of mast cells are activated too easily.

A trigger to release their contents, called mediators, these mediators can cause a variety of unpredictable symptoms in both children and adults, including skin rash, redness, abdominal pain, bloating, nausea, vomiting, headache, bone pain and skeletal injuries, and anaphylaxis.

Triggers can be heat, cold, stress (physical or emotional), perfumes or smells, medications, insect bites, and food.

These symptoms are treated with medications including antihistamines, mast cell stabilizers, and leukotriene inhibitors, while anaphylaxis is a medical emergency that requires epinephrine.

Mastocytosis can affect the skin and internal organs, such as the bone marrow, gastrointestinal tract, liver, and spleen.

Most patients with mastocytosis have benign or cutaneous systemic forms, but it can develop into an aggressive disease that may require chemotherapy.

Allergic disease

Many forms of skin and mucosal allergy are largely mediated by mast cells, they play a central role in asthma, eczema, itching (from various causes), and allergic rhinitis and allergic conjunctivitis.

Antihistamine medications work by blocking the action of histamine on nerve endings.

Cromolyn-based drugs (cromolyn sodium, nedocromil) block a calcium channel essential for mast cell degranulation, stabilizing the cell and preventing the release of histamine and related mediators.

Leukotriene antagonists (such as montelukast and zafirlukast) block the action of leukotriene mediators and are increasingly used in allergic diseases.

Anaphylaxis

In anaphylaxis (a severe systemic reaction to allergens, such as nuts, bee stings, or medications), degranulation of mast cells throughout the body results in vasodilation and, if severe, symptoms of life-threatening shock.

Autoimmunity

Mast cells are involved in the pathology associated with autoimmune disorders, rheumatoid arthritis, bullous pemphigoid, and multiple sclerosis.

They have been shown to be involved in the recruitment of inflammatory cells in the joints such as rheumatoid arthritis and in the skin such as bullous pemphigoid, and this activity is dependent on antibodies and complement components.

Reproductive disorders

Mast cells are present within the endometrium, with increased activation and release of mediators in endometriosis.

In males, mast cells are present in the testes and end in oligo and azoospermia, as mast cell mediators directly suppress sperm motility in a potentially reversible manner.