A mast cell or mastocyte is formed from precursor cells in the bone marrow and depend upon stem cell factor for their survival. Immature mast cells are released from the bone marrow into the blood. The precise characteristics of the mast cell are possibly determined by the tissue site in which it eventually settles. Mast cells are found resident throughout the body, particularly in association with structures that are in close proximity to surfaces that interface to the external environment. They are especially prominent near the skin, the mucosa of the lungs and digestive tract, mouth, conjunctiva and nose.
Although best known for their role in allergies and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens. Mast cells settle mainly in connective tissue and usually do not circulate in the blood stream unless they are activated by a stimulus. Triggers of mast cells include bacteria (E-coli), chemicals (detergents, food additives/preservatives and xenoestrogines), drugs (local anesthetics, neuromuscular blockers and opiods), hormones (adrenocorticotropic hormone, estradiol) and physical conditions (cold, exercise, and pressure).
Mast cells are closely associated with Basophils which represent 0.5% of the white blood cell population. Basophils are also produced in the bone marrow but they tend to remain in the blood circulation unless adequately stimulated to settle in tissues. Both cells contain many granules rich in histamines and heparin. Heparin is an anti-clotting protein and histamine is a chemical found in damaged tissues that is involved in inflammation.
Heparin helps to prevent blood clotting in undamaged cells. It is present in low concentrations in the blood plasma and is produced by the mast cells found in the connective tissue and liver. It serves to prevent conversion of prothrombin into thrombin, and fibrinogen into fibrin, which are the enzymes that cause blood clots. Heparin is therefore widely used clinically as an anti-coagulant. If heparin granules are not released, blood clots or thrombus may form within the blood circulation and result in a medical condition known as thrombosis. Coronary thrombosis, a thrombus developing in the coronary artery of the heart, is very dangerous and can lead to a swift death.
When an area of the body is wounded or infected, the tissue surrounding the wound becomes swollen and painful. This is called inflammation and is due to the escape of chemicals, such as histamine, from the damaged tissue. This causes local vasodilation of capillaries which increases the amount of blood in the area and raises the temperature locally. Leakiness of the capillaries is also increased, permitting escape of plasma and white blood cells into the surrounding tissues, and a consequent swelling of the area: a condition known as oedema. Blood plasma contains antibodies, phagocytes and other chemicals, which causes inhibited growth or death of bacteria. This helps to combat the spread of infection, thereby protecting the body.
Allergies are a disorder of the immune system caused mainly by environmental factors, but some can be genetically related. Allergies are a form of hypersensitivity to a stimulus which results in excessive activation of the degranulation of mast cells and basophils. This activation is caused by the antibody Immunoglobulin E (IgE) and results in extreme inflammatory response. Mast cells have a high affinity receptor for the Fc region of IgE antibody. IgE, like all antibodies, are specific to one antigen.
When a person comes into contact with an allergen such as pollen for the first time, he or she makes large amounts of pollen IgE antibodies which attach themselves to mast cells. The second time that person encounters the pollen allergen the IgE primed mast cells release granules and powerful chemical mediators, such histamine and cytokines, into the environment. These chemical mediators cause the characteristic symptoms of an allergy such as itching, runny nose, pain and inflammation. Itching and pain usually results from the irritation of nerve endings.
Sometimes, there may be a severe systemic reaction to an allergen such as nuts, bee stings and drugs (e.g. penicillin) which causes degranulation of mast cells throughout the entire body. This condition, known as anaphylaxis, leads to vasodilation and severe shock which can be life threatening. The enhanced secretion of mast cells and basophils at sites of inflammation can accelerate the elimination of the cause of tissue injury or, paradoxically, may lead to a chronic inflammatory response. Thus, manipulating mast-cell and basophil adhesion may be an important strategy for controlling the outcome of allergic and inflammatory responses.
Antihistamine drugs act by blocking the action of histamine on nerve endings. Cromoglicate based drugs block the calcium channels essential for mast cell degranulation, stabilizing the cell and preventing release of histamine and related mediators.
Mast cell disorders, such as mast cell tumors or over proliferation of mast cells, can result in symptoms such as skin lesions, abdominal discomfort, very low blood pressure, shock, faintness, nausea, vomiting, and bone and muscle pain. These symptoms are usually a sign of mastocytosis, which is the spread of these mast cells throughout the body. This can cause the release of a large amount of histamine at one time resulting in ulceration of the stomach and duodenum, or disseminated intravascular coagulation. When metastasis (spreading of the tumor) does occur, it is usually to the liver, spleen, lymph nodes and bone marrow.
Mast cells, therefore, have the ability to be one of the most versatile cells in the body, owing to their ubiquitous location and the plethora of the active molecules produced. It can be said that mast cells release two major substances, heparin and histamine, which are in granular form. When these substances are degranulated or activated, allergic reactions and inflammation can occur. Mast cells are needed to assist the body in its defense against foreign substances since its degranulation alerts the body that something is wrong and the necessary defense mechanisms in the body are activated. Therefore, mast cells play an important role in leading the immune reaction to an effective immune defense. Without mast cells, blood clots will freely occur throughout the body resulting in death of surrounding cells and eventually death of the organism.
