Mast cell

A mast cell is a type of white blood cell that protects the body from immune threats by promoting inflammation. Mast cells are present in all tissues but especially connective tissues. They are also found in the brain, in particular along the blood-cerebrospinal fluid barrier. They are most commonly known for their role in the immune system of mucosal membranes; however, they are necessary in maintaining basic human health and defending against pathogens.

When a mast cell encounters a 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 they encounter a foreign substance. A cascade response allows for degranulation to begin and a subsequent release of inflammatory granules into the bloodstream.

Inhibition
One study found that acetylcholine via muscarinic receptors strongly inhibited the release of histamine in mucosal mast cells.

Infection
Past findings have suggested that mast cell activation due to a viral infection may play a part in initiating autoimmune disease. Coxsackievirus infection has been observed to up-regulate toll-like receptor 4 (TLR4) on mast cells in mice, immediately following the period of infection. TLR4 up-regulation may have negative consequences on the immune system because TLR4 up-regulation may activate the innate immune system and the inflammatory response system.

Physical stress
Mast cells are distributed throughout the nervous system, including in the dura, and are known to degranulate when nervous tissue is stretched. They also activate in response to vibration.

Potential treatments
There are several proposed supplements or treatments that might grant temporary mast cell degranulation inhibition:

Antioxidants: these are substances that are considered to remove potentially harmful reactive oxygen species from the body. Vitamin C, vitamin A, vitamin E, and beta-carotene are examples of antioxidants. The properties of such antioxidants have been noted to be capable of reducing blood histamine levels. The exact mechanisms that cause blood histamine levels to decrease are still unknown. However, antioxidants have been noted to be capable of inhibiting mast cell production and altering the enzymes that form (diamine oxidase) or breakdown (histidine decarboxylase) histidine.

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

Role in the human body
Mast cells are found within the nervous system and are capable of crossing the blood-brain barrier, which separates blood from the central nervous system. The gastrointestinal tract and the brain are capable of communicating through the blood brain barrier, also known as the gut-brain axis (GBA). Exchange of information between the central (brain) and peripheral (gut) nervous systems ensures that the stomach and intestines are communicating with the brain. "Immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling" are all influenced by the GBA. Therefore mast cells may be a type of cell that indirectly affects neurological functioning when the gut is inflamed.

Like the tissue-resident macrophages known as microglia, but unlike other bone marrow-derived cells of the immune system, mast cells naturally occur in the human brain where they interact with the neuroimmune system. In the brain, mast cells are located in a number of structures that mediate visceral sensory (e.g., pain) or neuroendocrine functions or that are located along the blood–cerebrospinal fluid barrier, including the pituitary stalk, pineal gland, thalamus, and hypothalamus, area postrema, choroid plexus, and in the dural layer of the meninges near meningeal nociceptors. Mast cells serve the same general functions in the body and central nervous system, such as effecting or regulating allergic responses, innate and adaptive immunity, autoimmunity, and inflammation. Across systems, mast cells serve as the main effector cell through which pathogens can affect the gut–brain axis.

Mast cell activation syndrome
Mast cell activation syndrome (MCAS) is a condition in which mast cells are over-responsive to various environmental triggers. When mast cells are over-responsive the result can be an increase in the release of histamine and other inflammatory molecules. Excessive inflammation can result from such a condition.

MCAS 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. The overlap between EDS, POTS, and MCAS is thought to be due to increased tryptase production owing to an extra copy of a gene called TPSAB.

MCAS should be distinguished from mastocytosis, a genetic disorder causing excessive production of mast cells.

Myalgic Encephalomyelitis
Research on the relationship between mast cells and ME is in its infancy. One study found that individuals diagnosed with moderate to severe ME have been noted to have higher amounts of dysfunctional mast cells in circulation.

At a two-day physician summit in Salt Lake City, Utah March 2018, physicians discussed the relationship between “Chronic Fatigue Syndrome” and mast cell activation syndrome.
 * David Kaufman: "ME/CFS is a descriptive diagnosis of a bunch of symptoms, but it says nothing about what's causing the symptoms, which is probably part of the reason it's so hard for it to get recognition. So, the question becomes, What other pathology is driving this illness and making the person feel so ill? I think mast cell activation is one of those drivers, whether cause, effect, or perpetuator, I don't know."
 * Charles Lapp: "I see a lot of this. I think it's one of the many overlap syndromes that we've been missing for years."
 * Susan Levine: "I suspect 50% to 60% of ME/CFS patients have it. It's a very new concept."...In Levine's experience, MCAS often manifests in patients being unable to tolerate certain foods or medications. "If we can reduce the mast cell problem, we can facilitate taking other drugs to treat ME/CFS," she said. However, she also cautioned, "It's going to be a subset, not all ME/CFS patients."

Fibromyalgia
Over expression of mast cells has been observed in the skin of patients with fibromyalgia.

Notable studies

 * 2017, Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients - (Full Text)