Mast cell

A mast cell is a type of white blood cell that exerts pro-inflammatory functions and serves immunoregulatory roles. Mast cells are present in all tissues and are most commonly known for their role in the mucosal immune system; however, they are necessary in maintaining physiological homeostasis and preventing pathogenesis throughout the body.

When a mast cell encounters an antigen or perceived immune threat, pro-inflammatory mediators are released through a process known as degranulation. Some anti-inflammatory mediators may include histamine, cytokines, proteases, or heparin.

Degranulation
Mast cells can become activated when their associated antibody receptors come in direct contact with an antigen. A cascade response allows for degranulation to begin and a subsequent release of inflammatory granules into the bloodstream.

Mechanisms of Inhibition
There are several proposed supplements or treatments that might grant temporary mast cell degranulation inhibition through various mechanisms.

Antioxidants: Vitamin C reduces blood histamine levels, potentially through several mechanisms: by inhibiting mast cell production; by increasing diamine oxidase (an enzyme that breaks down histamine); by inhibiting mast cell degranulation (and the release of histamine in the first place), and by inhibiting histidine decarboxylase (the enzyme that forms histamine). Ultraviolet B light induced histamine release from mast cells in rats in a dose-dependent manner, and was inhibited by Vitamin C. Vitamin B6 is also a diamine oxidase cofactor.

Phototherapy: UVA and UVA1 phototherapy has been observed to significantly inhibit histamine release from mast cells and other white blood cells.

Moreover, UV light, especially UVB, has also been reported to be able to trigger allergic reaction, leading to mast cell degranulation and histamine release [10]. Thus, compounds possessing protective activities against UVB light may influence its anti-allergic properties via the inhibition of mast cell degranulation and histamine release

Infection
In a mouse model of myocarditis, Coxsackievirus infection was found to up-regulate Toll-like receptor 4 on mast cells and macrophages immediately following infection. It also increased numbers of mast cells.

Nervous system
Mast cells play an important role in the gut-brain axis of the peripheral nervous system. They are found throughout the gastrointestinal tract near sensory nerve fibers, such as the sensory vagus nerve. In the central nervous system, they are found on the blood-brain barrier, in the dural layer of the meninges, and in areas of the brain responsible for pain or neuroendocrine functions including the pituitary stalk, pineal gland, thalamus, and hypothalamus.

They are a primary type of effector cell though which intestinal pathogens can affect the brain.

Mast cells are found within the blood-brain barrier, in the dural layer of the meninges, and in areas of the brain responsible for pain and neuroendocrine functions including the pituitary stalk, pineal gland, thalamus, and hypothalamus.

Mast cells play an important role in the gut-brain axis (GBA) of the peripheral nervous system. The gastrointestinal tract and the brain are capable of bidirectional communication through what is known as the GBA; This allows for exchange of information between the central and peripheral nervous systems. GBA communication ensures the integration of gut homeostasis with emotional and cognitive centers of the brain. "Immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling" are all influenced by the GBA. This means that mast cells that are found throughout the gastrointestinal tract and near sensory nerve fibers, such as the sensory vagus nerve, have the capability to cross the GBA and enter the central nervous system. Therefore mast cells are perhaps a type of effector cell though which intestinal pathogens can communicate with and effect neurological functioning.

Mast cell activation disorder
See full article: Mast cell activation disorder

Mast cell activation disorder (MCAD) is a disorder where mast cells are normal in number but over-responsive to dietary and environmental triggers. Cells release excess histamine and other signaling molecules, causing symptoms. It is often found in patients with Ehlers-Danlos syndrome (EDS) and postural orthostatic tachycardia syndrome (POTS), a form of orthostatic intolerance, two conditions commonly co-morbid with ME/CFS. The overlap between EDS, POTS, and MCAD is thought to be due to increased tryptase production owing to an extra copy of a gene called TPSAB1.

MCAD should be distinguished from mastocytosis, a genetic disorder of excessive populations of mast cells.

Chronic fatigue syndrome
One study found that moderate and severe ME/CFS patients had higher levels of naive mast cells than healthy controls. Clinicians increasingly believe that mast cells underly the dysfunction found in the disease.

Notable studies

 * 2016, Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients (Donald Staines, Sonya Marshall-Gradisnik)