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.
- 1 Mast cell activation
- 2 Activating factors
- 3 Inhibitory factors
- 4 Role in the human body
- 5 Role in human disease
- 6 Notable studies
- 7 See also
- 8 Learn more
- 9 References
Mast cell activation[edit | edit source]
Activation[edit | edit source]
Degranulation[edit | edit source]
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[edit | edit source]
Activating factors[edit | edit source]
Infection[edit | edit source]
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.
Sex hormones[edit | edit source]
Physical stress[edit | edit source]
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.
Inhibitory factors[edit | edit source]
Potential treatments[edit | edit source]
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[edit | edit source]
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.
Role in human disease[edit | edit source]
Mast cell activation syndrome[edit | edit source]
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[edit | edit source]
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[edit | edit source]
Over expression of mast cells has been observed in the skin of patients with fibromyalgia.
Endometriosis[edit | edit source]
Notable studies[edit | edit source]
- 2017, Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients - (Full Text)
See also[edit | edit source]
Learn more[edit | edit source]
References[edit | edit source]
- Krystel-Whittemore, M; Dileepan, KN; Wood, JG (2016). "Mast Cell: A Multi-Functional Master Cell". Front. Immunol. 6: 620. doi:10.3389/fimmu.2015.00620.
- Reinheimer, T.; Baumgärtner, D.; Höhle, K.D.; Racké, K.; Wessler, I. (1997). "Acetylcholine via Muscarinic Receptors Inhibits Histamine Release from Human Isolated Bronchi". American Journal of Respiratory and Critical Care Medicine. doi:10.1164/ajrccm.156.2.96-12079#.v7vo-zmrlmv.
- Fairweather, D. (2005). "Viruses as adjuvants for autoimmunity: evidence from Coxsackievirus-induced myocarditis". Rev Med Virol.
- Skaper, Stephen D.; Facci, Laura; Giusti, Pietro (March 2014). "Mast cells, glia and neuroinflammation: partners in crime?". Immunology. 141 (3): 314–327. doi:10.1111/imm.12170. ISSN 1365-2567. PMC 3930370. PMID 24032675.
- Hu, Kenneth K.; Bruce, Marc A.; Butte, Manish J. (May 1, 2014). "Spatiotemporally and mechanically controlled triggering of mast cells using atomic force microscopy". Immunologic Research. 58 (2): 211–217. doi:10.1007/s12026-014-8510-7. ISSN 1559-0755. PMC 4154250. PMID 24777418.
- Tettamanti, L (2018). "Different signals induce mast cell inflammatory activity: inhibitory effect of Vitamin E.". J biol regul homeost agents.
- Kronauer, C (2007). "Influence of UVB, UVA and UVA1 Irradiation on Histamine Release from Human Basophils and Mast Cells In Vitro in the Presence and Absence of Antioxidants". Photochemistry and Photobiology.
- Carabotti, Marilia; Scirocco, Annunziata; Maselli, Maria Antonietta; Severi, Annunziata (2015). "The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems". Ann Gasteroenterol. 28 (2): 203–209. PMC 4367209. PMID 25830558.
- Polyzoidis S, Koletsa T, Panagiotidou S, Ashkan K, Theoharides TC (2015). "Mast cells in meningiomas and brain inflammation". J Neuroinflammation. 12 (1): 170. doi:10.1186/s12974-015-0388-3. PMC 4573939. PMID 26377554.
MCs originate from a bone marrow progenitor and subsequently develop different phenotype characteristics locally in tissues. Their range of functions is wide and includes participation in allergic reactions, innate and adaptive immunity, inflammation, and autoimmunity . In the human brain, MCs can be located in various areas, such as the pituitary stalk, the pineal gland, the area postrema, the choroid plexus, thalamus, hypothalamus, and the median eminence . In the meninges, they are found within the dural layer in association with vessels and terminals of meningeal nociceptors . MCs have a distinct feature compared to other hematopoietic cells in that they reside in the brain . MCs contain numerous granules and secrete an abundance of prestored mediators such as corticotropin-releasing hormone (CRH), neurotensin (NT), substance P (SP), tryptase, chymase, vasoactive intestinal peptide (VIP), vascular endothelial growth factor (VEGF), TNF, prostaglandins, leukotrienes, and varieties of chemokines and cytokines some of which are known to disrupt the integrity of the blood-brain barrier (BBB) [38–40]...
[The] key role of MCs in inflammation  and in the disruption of the BBB [41–43] suggests areas of importance for novel therapy research. Increasing evidence also indicates that MCs participate in neuroinflammation directly [44–46] and through microglia stimulation , contributing to the pathogenesis of such conditions such as headaches,  autism , and chronic fatigue syndrome . In fact, a recent review indicated that peripheral inflammatory stimuli can cause microglia activation , thus possibly involving MCs outside the brain.
- Aguzzi, A.; Barres, B.A.; Bennett, M.L. (January 11, 2013). "Microglia: Scapegoat, Saboteur, or Something Else?". Science. 339 (6116): 156–161. doi:10.1126/science.1227901. ISSN 0036-8075.
- Budzyński, Jacek; Kłopocka, Maria (May 14, 2014). "Brain-gut axis in the pathogenesis of Helicobacter pylori infection". World Journal of Gastroenterology. 20 (18): 5212–5225. doi:10.3748/wjg.v20.i18.5212. ISSN 2219-2840. PMC 4017036. PMID 24833851.
- Milner, Joshua, Dr. "Research Update: POTS, EDS, MCAS Genetics." 2015 Dysautonomia International Conference & CME. Washington DC. Dysautonomia International Research Update: POTS, EDS, MCAS Genetics. Web. <https://vimeo.com/142039306>
- Cheung, Ingrid (February 2015). "A New Disease Cluster: Mast Cell Activation Syndrome, Postural Orthostatic Tachycardia Syndrome, and Ehlers-Danlos Syndrome". The Journal of Allergy and Clinical Immunology.
- Nguyen, T.; Johnston, S.; Chacko, A.; Gibson, D.; Cepon, J.; Smith, D.; Staines, D.; Marshall-Gradisnik, S. (2017). "Novel characterisation of mast cell phenotypes from peripheral blood mononuclear cells in chronic fatigue syndrome/myalgic encephalomyelitis patients". Asian Pac J Allergy Immunol. 35 (2): 75-81. doi:10.12932/AP0771.
- "Mast Cell Activation May Underlie 'Chronic Fatigue Syndrome'". Medscape. March 13, 2018. Retrieved September 25, 2018.
- Ang, D.C.; Hilligoss, J.; Stump, T. (2015). "Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial". The Clinical Journal of Pain. 31 (9): 836–842. PMC 4417653. PMID 25370135.
membrane The word "membrane" can have different meanings in different fields of biology. In cell biology, a membrane is a layer of molecules that surround its contents. Examples of cell-biology membranes include the "cell membrane" that surrounds a cell, the "mitochondrial membranes" that form the outer layers of mitochondria, and the "viral envelope" that surrounds enveloped viruses. In anatomy or tissue biology, a membrane is a barrier formed by a layer of cells. Examples of anatomical membranes include the pleural membranes that surrounds the lungs, the pericardium which surrounds the heart, and some of the layers within the blood-brain barrier.
β β / Β. Greek letter beta (a symbol used in science), equivalent to "b".
enzyme a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.
postural orthostatic tachycardia syndrome (POTS) - A form of orthostatic intolerance where the cardinal symptom is excessive tachycardia due to changing position (e.g. from lying down to sitting up).
myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.
microglia A type of immune cell, called a macrophage, that lives in the brain. For historical reasons, macrophages have different names based on the part of the body that they normally live in. Macrophages that normally live in the blood are called monocytes. Macrophages that normally live in the skin are called Langerhans cells. Macrophages that normally live in the liver are called Kupffer cells. And macrophages that normally live in the central nervous system are called microglia. Microglia were originally classified as glial cells, under the assumption that the cells had a merely structural function, before it was realized that the cells were in fact immune cells. As the "sentinel cells" of the central nervous system, microglia survey their environment for abnormalities such as infection or tissue damage, and then initiate an immune response to fight the infection or repair the tissue damage.
dysautonomia disorders of the autonomic nervous system that cause disturbances in all or some autonomic functions, may cause problems regulating autonomic functions, including heart rate, blood pressure, body temperature, and digestion. Can cause symptoms including lightheadedness, fainting, unstable blood pressure, and orthostatic intolerance.