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mast cell biology

Mast cell interactions with B and T cells

Mast cells communicate with many other cells of various types in the body. The type of communication we have discussed here most often is via mediator release – mast cells release mediators and they trigger an action in another cell by binding to a receptor, or the other cells release mediators that act on mast cell receptors. Another method of interaction is for cells to physically contact with each other. Mast cells use these techniques to impact the behavior of other cells.

B cells are lymphocytes, a kind of white blood cell. They form part of the adaptive immune system, the arm of immunity that is learned over the course of your life. They make antibodies when exposed to allergens or antigens from infectious agents. They help amplify the immune response during infection, can release cytokines and some become memory B cells, which allow for rapid response to a previously encountered organism.

Mast cells produce and release IL-4, IL-5, IL-6 and IL-13, all of which regulate the development of B cells and which role they develop toward. Mast cells can induce IgE production by B cells via binding of OX40 on the B cell to the OX40 receptor on the mast cell. In the absence of an activating signal, mast cells are able to cause unactivated B cells to proliferate and become IgM producing cells.

Resting and activated mast cells inhibit B cell death and promote proliferation of undifferentiated B cells. When the B cells are activated, this effect is exaggerated. These changes occur when mast cells and B cells are in contact and mast cells have released IL-6. Activated mast cells can drive B cells toward becoming CD138+ plasma cells or producing IgA.

T cells are also lymphocytes. There are several types of T cells and all perform very specialized functions. Mast cells and T cells are often found in close physical proximity in inflamed spaces. Conditions in which this commonly occurs include sarcoidosis, irritable bowel disease, rheumatoid arthritis and prolonged allergic processes.

Contact between mast cells and T cells initiates gene expression in mast cells. When the T cells are activated, it also induces mast degranulation, production/release of TNFa, release of MMP-9, inhibition of MMP-1, and release of IL-4 and IL-6. This occurs due to binding between the surface molecules LFA-1 and ICAM-1. Another receptor on mast cell surfaces, LTβR, can be bound by T cells. This initiates release of IL-4, IL-6, TNFa, CXCL2 and CCL5 by mast cells. In the presence of TNFa, binding to OX40 on activated CD4+ T cells by mast cells causes T cell proliferation and cytokine production.

Mast cells can express proteins on their surfaces called major histocompatibility complex I and II. These proteins literally show pieces of a phagocytosed, or “eaten”, pathogen. Showing these pieces to other cells allows them to fight infection in a specialized way. When mast cells express MHC II, they can steer T cells toward developing into specific types, including Treg cells. When mast cells express MHC I, they increase CD8+ T cell populations and ability to kill infectious agents. CD8+ T cells can cause MHC I expression by mast cells.

Mast cells and Treg cells are found in close proximity in secondary lymphoid and mucosal tissues. Activated Treg cells reduce the amount of IgE receptors on mast cells when they come into contact. They also cause release of TGF-b and IL-10. Treg cells interfere with degranulation via the OX40 receptor on mast cells.


Gri, Giorgia, et al. Mast cell: an emerging partner in immune interaction. Front. Immunol., 25 May 2012.

Brill, A., Baram, D., Sela, U., Salamon, P., Mekori, Y. A., and Hershkoviz, R. Induction of mast cell interactions with blood vessel wall components by direct contact with intact T cells or T cell membranes in vitro. Clin. Exp. Allergy 2004; 34, 1725–1731.


Mast cells in kidney disease

Kidneys are essentially large filters. Blood is passed through endothelial cells in blood vessels, then filtered through a membrane made up of structural molecules. The filtrate then moves into kidney tubules where it becomes urine and is pushed out towards the bladder. During this process, the kidneys carefully remove substances from urine and put other substances into it in order to regulate available water, electrolyte concentration and blood pressure.

Chronic kidney disease can be caused by a variety of insults, including diabetes, high blood pressure, genetic conditions, chemical exposure, damage from shock, autoimmune disease and infections. Regardless of the underlying reason, once the kidney is injured, it can become sclerosed and fibrosed if not healed correctly. This can ultimately cause kidney failure. The kidney is able to function well even when a significant portion is damaged. For this reason, kidney disease is often not identified until 60-70% of functional kidney cells have been damaged beyond repair.

Mast cells have very complex and nuanced roles in renal disease. In healthy kidneys, mast cells are rare. In the presence of kidney disease, mast cells form a significant infiltrate, with counts increasing by as much as 60 times compared to healthy controls. IgA nephropathy, lupus nephritis, diabetic nephropathy and renal tubulointerstitial fibrosis are all conditions in which mast cell count has been correlated with degree of kidney fibrosis. Mast cell growth factors such as stem cell factor (SCF) are elevated in affected kidney tissue. However, mast cell count has not been shown to be related to severity of disease in any models thus far.

Mast cells are not the only allergic actor involved in kidney disease. Atopy (having allergic conditions like atopic dermatitis or allergic asthma) has been linked to idiopathic nephrotic syndromes in which patients experience kidney damage for unknown reasons. These patients often have multiple severe allergies and have serum IgE levels higher than found in other kidney diseases. Furthermore, IgE levels stay high in patients that relapse. Allergy immunotherapy and trigger avoidance has been trialed in these patients with mixed results. Many researchers believe that in these patients, the nephritis and allergies are both manifestations of one underlying condition.

IgE levels are also increased in nephritis caused by lupus (SLE). Basophils, different cells involved in allergies, make antibodies to IgE, causing an inflammatory response and worsening this type of nephritis.

Kidney damage can be caused by heavy metals and chemicals, including some types of chemotherapy. Tryptase is significantly elevated in patients with this kind of damage. In these patients, neutrophils and CD4+ T cells quickly infiltrate affected kidney tissue. In animal models where they are mast cell deficient, this infiltration by neutrophils and T cells is less efficient. This means that mast cells are involved in drawing these cells to the kidney. Treatment of the tissue with cromolyn also decreases the level of infiltration.

Mast cells are known to participate in fibrosis both in the kidney and elsewhere. Mast cells release fibrosis driving molecules like type VIII collagen in diabetic nephropathy; fibroblast growth factor in IgA nephropathy; and release tryptase, chymase and carboxypeptidase A, which participate in remodeling and fibrosis, in a number of conditions. Tryptase can also cause proliferation of fibroblasts.

Fibrosis develops largely due to the activity of TGFb and angiotensin II, which can be regulated by mast cells. Chymase can generate angiotensin II, which increases blood pressure and can further aggravate kidney conditions. In biopsies for which chymase staining is positive, fibrosis is significant. Renin, a molecule that regulates angiotensin II, is also released by mast cells.

In spite of these data, there is also significant evidence that in some instances, mast cells are protective against kidney disease. In some research models where mast cells are deficient or absent, kidney damage progresses more quickly. Levels of IL-4 and TGFb1, which can drive kidney damage, are higher in mast cell deficient models. Heparin, a mast cell mediator, is known to interfere with production of TGFb1.

In some cases, mast cells even protect against kidney fibrosis. Mast cells have been found to degrade fibronectin, which other cells need to filtrate the kidney. Mast cells can also prevent deposition of fibrin and type I collagen, which contributes to fibrosis.


Madjene, LC., et al. Mast cells in renal inflammation and fibrosis: Lessons learnt from animal studies. Molecular Immunology 63 (2015) 86-93.

Blank, U., et al. Mast cells and inflammatory kidney disease. Immunol Rev 2007, 217: 79-95.

Summers, SA., et al. Mast cell activation and degranulation promotes renal fibrosis in experimental unilateral ureteric obstruction. Kidney Int 2012.

Regulation of mast cells by IgE and stem cell factor (SCF)

Mast cells are regulated by two dominant mechanisms. The first is the allergic response via the high affinity IgE receptor. This receptor is called FcεRI. When an IgE molecule binds to this receptor, it triggers the release of calcium in pockets inside the cells, causes the cells to take up more calcium from outside the cell, and changes the cell membrane so that it can degranulate and secrete mediators. There are a number of other things that can affect the strength of the response triggered by FcεRI.

The second mechanism is the survival and activation response when stem cell factor (SCF) binds to the CKIT receptor (also called KIT). SCF is the primary growth and survival factor in non-neoplastic mast cells. In the absence of mast cell disease, it is absolutely required for survival. SCF also attracts mast cells and enhances degranulation from the FcεRI (IgE) receptor, production of cytokines and movement of mast cells from one place to another.

When SCF is increased in tissues, it increases the amount of mast cells there, how long they live and what roles they play. It also increases mast cell responsiveness. In some instances, SCF can directly cause degranulation with IgE involvement.

Despite understanding the importance of SCF, it is not well understood what happens after SCF binds to the CKIT receptor. We know that it increases survival and proliferation, but it’s not clear how. It is possible that the concentration of SCF or CKIT may play a role.

In tissues, mast cells often exist as a part of a membrane, and SCF is important in mast cell adhesion to other cells. When SCF is part of that membrane, it can increase histamine and eotaxin production in mast cells.

Monomeric IgE is IgE that is not bound to an allergen. In the presence of SCF, monomeric IgE can directly cause release of histamine, LTC4 and IL-8. It also makes mast cells more reactive.   When monomeric IgE binds to the FcεRI (IgE) receptor without SCF present, it causes production of IL-6 but not degranulation. However, IL-6 promotes mast cell survival.


Cruse, G., Bradding, P. Mast cells in airway dieases and institial lung disease. Eur J Pharmacol (2015).

River, K., Gilfillian, A.M. Molecular regulation of mast cell activation. J Allergy Clin Immunol 2006, 117, 1214-1225.

Gilfillian, A.M., Beaven, M.A. Regulation of mast cell responses in health and disease. Crit Rev Immunol 2011, 31, 475-529.


Mast cells in vascular disease: Part 3

Aneurysms are formed when elastic tissue is degraded by proteases and MMPs; the vessel is thinned due to smooth muscle loss; and the endothelium is broken down, resulting in inflammation. There is a significant body of evidence linking aneurysm formation and growth to mast cell activity.

A number of studies have found that mast cells are present in larger numbers in vasculature near aneurysms. Mast cells are increased in cerebral arteries of patients who died from subarachnoid hemorrhage. In particular, mast cell number is higher in arteries close to the rupture site. Mast cell count has been linked previously to aneurysm instability. Another study found that activated mast cells were increased in the aortas of patients who died from abdominal aortic aneurysms. Increased mast cells are also found in ascending aortic aneurysms. Mast cell density is a predictor for occurrence of ascending aortic aneurysm.

Chymase activity has been heavily implicated in aneurysm physiology. One study found that levels of angiotensin II were unlikely to induce development of aneurysm, but that degradation of the vessel by chymase may weaken the aneurysm and increase risk of rupture. Increased chymase activity was found in an additional fourteen patients having aortic aneurysms repaired. In thoracic aortic aneurysm patients, chymase positive mast cells were found in inflamed areas. Chymase may participate in the generation of reactive oxygen species. In abdominal aortic aneurysm samples, most players in the renin-angiotensin system, including chymase and cathepsins, are increased.

Serpin A3, a protease inhibitor, normally regulates activity of elastase, chymase and cathepsin G. It is thought that deficiency of this molecule may worsen damage caused by chymase.

Mast cell proteases, like tryptase and chymase, may be involved in the formation of aneurysms. Erosion of the endothelium occurred in the thrombosed region of the vessel, followed by decreased oxygen supply to the underlying vessel. Tryptase and chymase may participate in rupture of the vessel and intravascular hemorrhage. Adrenomedullin, a mast cell mediator, is found to be strongly expressed in mast cells to local to aneurysms. Adrenomedullin suppresses formation of the extracellular matrix.

Serum tryptase levels in abdominal aortic aneurysms correlated well with growth of aneurysm as well as risk of complications during repair. Tryptase deficient mice were completely protected against developing this type of aneurysm. Tryptase deficiency reduced expression of cathepsins, as well as activation of endothelial cells and movement of monocytes. Tryptase induces release of cathepsins that trigger apoptosis, so this may be a mechanism.

5-lipoxygenase is the enzyme that drives leukotriene formation. Mice deficient in this molecule were protected against aneurysm formation. They also had less inflammation and apoptosis, lower IL-6 and IFN-γ. Mast cell degranulation augmented aneurysm formation while mast cell stabilizer cromolyn decreased it. Another study found that treatment with tranilast, another mast cell stabilizer, decreased the diameter of the aorta.

Leukotriene C4 and 5-lipoxygenase are increased in patients with abdominal aortic aneurysms, but leukotriene B4 is not. Leukotrienes increase release of MMPs and encourage matrix degradation. Leukotrienes may be a therapeutic target to slow aneurysm progression.


Kennedy, Simon, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 138 (2013) 53-65.

Bot, Ilze, et al. Mast cells: Pivotal players in cardiovascular diseases. Current Cardiology Reviews, 2008, 4, 170-178.


Mast cells in wound healing

One of the most well described non-allergic functions of the mast cell is wound healing. Mast cells are involved in many functions integral to remodeling and closing wounds.

Immediately following formation of a wound, signals are sent to constrict vessels near the injury to decrease the risk of bleeding and infection. After bleeding has been minimized, the blood vessels become a little more permeable to let cells and molecules from the bloodstream into the injured area in order to promote healing and prevent infection. These actions activate the complement clotting system, which produces molecules C3a and C5a. These molecules bind to mast cells and induce degranulation.

Following degranulation, vessels become more permeable through the action of histamine and other mediators. Fibrinogen, important in clot formation, leaves the blood stream and accumulates in the tissue. This triggers thrombin to change fibrinogen to fibrin, forming a clot. Mast cells are active in preventing excessive clotting. Tryptase and heparin are released from granules bound together, and this complex degrades fibrogen and inactivates thrombin.

The extracellular matrix is the structures which give substance to groups of cells and vessels. Following wound formation, fibronectin and type III collagen molecules gather near the injury. Mast cell proteases chymase and tryptase break down the extracellular matrix molecules to make room for newly made cells to close the wound. It is also possible that mast cell mediator CMA1 breaks down fibronectin.

Granulation tissue forms when wounds are healing. Granulation involves several activities, such as cell proliferation, develop of blood vessels, and building of new skin. Fibroblasts, which make collagen and extracellular matrix molecules, are drawn to the injury by mast cell signaling. Once there, they are induced to proliferate by action of the presence of histamine, tryptase, heparin and fibroblast growth factor. Mast cell degranulation also drives generation of new blood vessels through action of histamine, heparin, chymase, fibroblast growth factor, VEGF and tumor necrosis factor. Formation and proliferation of new epithelial tissue is also encouraged by TGF-b1, histamine, IL-1a, IL-1b, IL-6, tryptase, and heparin.

Once enough new cells have been made, the fibroblasts become myofibroblasts to make new muscle. Histamine and tryptase mediate this step. The fibroblasts directly interact with mast cells. Mast cell proteases tryptase and chymase trigger the activation of several molecules that mediate remodeling of the extracellular matrix. The wound is closed following this remodeling and laying down of new skin.


Douaiher, Jeffrey, et al. Development of Mast Cells and Importance of Their Tryptase and Chymase Serine Proteases in Inflammation and Wound Healing Advances in Immunology, Volume 122 (2014): Chapter 6.

Christine Möller Westerberg, Erik Ullerås, Gunnar Nilsson. Differentiation of mast cell subpopulations from mouse embryonic stem cells. Journal of Immunological Methods 382 (2012) 160–166.




Master table of stored mast cell mediators

Mediator Symptoms Pathophysiology
Angiogenin Tissue damage Formation of new blood vessels, degradation of basement membrane and local matrix
Arylsulfatases Breaks down molecules to produce building blocks for nerve and muscle cells
Bradykinin Angioedema, swelling of airway, swelling of GI tract, inflammation, pain, hypotension Vasodilation, induces release of nitric oxide and prostacyclin
Carboxypeptidase A Muscle damage Tissue remodeling
Cathepsin G Pain, muscle damage Converts angiotensin I to II, activates TGF-b, muscle damage, pain, fibrosis, activates platelets, vasodilation
Chondroitin sulfate Cartilage synthesis
Chymase Cardiac arrhythmia, hypertension, myocardial infarction Tissue remodeling, conversion of angiotensin I to II, cleaves lipoproteins, activates TGF-b, tissue damage, pain, fibrosis
Corticotropin-releasing hormone Dysregulation has wide reaching and severe effects Stimulates secretion of ACTH to form cortisol and steroids
Endorphins Numbness Pain relief
Endothelin Hypertension, cardiac hypertrophy, type II diabetes, Hirschsprung disease Vasoconstriction
Eotaxin (CCL11) Cognitive deficits Attracts eosinophils, decreases nerve growth
Heparin Hematoma formation, bruising, prolonged bleeding post-biopsy, gum bleeding, epistaxis, GI bleed, conjunctival bleeding, bleeding ulcers Cofactor for nerve growth factor, anticoagulant, prevents platelet aggregation, angiogenesis
Histamine Headache, hypotension, pruritis, urticaria, angioedema, diarrhea, anaphylaxis Vasodilation of vessels, vasoconstriction of atherosclerotic coronary arteries, action of endothelium, formation of new blood vessels cell proliferation, pain
Hyaluronic acid Degradation contributes to skin damage Tissue repair, cartilage synthesis, activation of white blood cells
IL-8 (CXCL8) Mast cell degranulation Attracts white blood cells (mostly neutrophils) to site of infection, activates mast cells, promotes degranulation
Kininogenases Angioedema, pain, low blood pressure Synthesis of bradykinin
Leptin Obesity Regulates food intake
Matrix metalloproteinases Irregular menses (MMP-2) Tissue damage, modification of cytokines and chemokines (modifies molecules to make them useful)
MCP-1 (CCL2) Nerve pain Attracts white blood cells to site of injury or infection, neuroinflammation, infiltration of monocytes (seen in some autoimmune diseases)
MCP-3 (CCL7) Increases activity of white blood cells in inflamed spaces
MCP-4 (CCL13) Shortness of breath, tightness of airway, cough Attracts white blood cells to inflamed spaces, induces mast cell release of TNFa and IL-1, asthma symptoms
Phospholipase A2 Vascular inflammation, acute coronary syndrome Generates precursor molecule for prostaglandins and leukotrienes
RANTES (CCL5) Osteoarthritis Attracts white cells to inflamed spaces, causes proliferation of some white cells
Renin Cardiac arrhythmias, myocardial infarction, blood pressure abnormalities Angiotensin synthesis, controls volume of blood plasma,lymph and interstitial fluid, regulates blood pressure
Serotonin/5-HT Nausea, vomiting, diarrhea, headache, GI pain Vasoconstriction, pain
Somatostatin Low stomach acid symptoms, low blood sugar Regulates endocrine system, cell growth and nerve signals, inhibits release of glucagon and insulin, decreases release of gastrin, secretin and histamine
Substance P Neurologic pain, inflammation, nausea, vomiting, mood disorders, anxiety Transmits sensory nerve signals, including pain, mood disorders, stress perception, nerve growth and respiration
Tissue plasminogen activator Blood clots Activates plasminogen, clotting
Tryptase Hematoma formation, bruising, prolonged bleeding post-biopsy, gum bleeding, epistaxis, GI bleed, conjunctival bleeding, bleeding ulcers; inflammation Activation of endothelium, triggers smooth muscle proliferation, activates degradation of fibrinogen, activates MMP molecules,tissue damage, activation of PAR, inflammation, pain
Urocortin Increased appetite when stressed, inflammation, low blood pressure Vasodilation, increases coronary blood flow
Vasoactive intestinal peptide Decreased absorption, low blood pressure, low stomach acid symptoms Vasodilation, mast cell activation, lowers blood pressure, relaxes muscles of trachea, stomach and gall bladder, inhibits gastric acid secretion, inhibits absorption
VEGF Diseases of blood vessels Formation of new blood vessels, vasodilation and permeability of smaller vessels

What do all these words mean? (Part 2)

What does it mean if a person is CD117 positive in a biopsy? Is this bad?

In the context of mast cell disease, it usually just means that mast cells were found.


If CD117 is normal for mast cells, why are people sometimes “negative for CD117” on biopsies?

This sometimes happens. When you have mast cell disease, you often have more CD117 receptors on mast cells. This makes it easier for the test to find them. So when you are found to be “negative for CD117” in regards to mast cell disease, you are not truly “negative”. You just express a lower amount of CD117 receptors so the test didn’t see them.


I am a mast cell patient and my bone marrow biopsy was positive for CD117. How do I know that it is normal mast cells that show CD117 and not these other dangerous cells you mentioned?

You can tell by looking at the cells with special stains. Pathologists and immunohistochemistry scientists are very skilled at distinguishing one cell type from another. They can tell based upon what the cell looks like in addition to being positive for CD117.


If I am CD117 positive in a biopsy, does that mean I am “CKIT positive”?

No. If I could do away with one single phrase in mast cell terminology, it would be CKIT+.

CKIT+ is a term used to mean “positive for the D816V mutation in codon 816 of the CKIT gene”. It means you are positive for a mutation that has been associated with neoplastic disorders of mast cells. So when people say they are CKIT+, they mean they were found to have a mutation. They do NOT mean they were found to have CKIT/CD117 on their mast cell surfaces, because this is totally normal and is the case for everyone.

Additionally, the test to detect CD117 on a cell surface is NOT the same test used to identify the D816V mutation. That test breaks open the cells and looks for a specific mutation in the DNA sequence. They are not run at the same time.


Why is it important to know if I am positive for the D816V mutation (CKIT+)?

The D816V mutation changes the shape of the CKIT receptor. Due to this wrong shape, the receptor does not need SCF to bind to the receptor to tell the mast cell to live longer. In this new shape, the receptor is stuck in an “activated” position, so it is telling the cell to live longer all the time, without SCF. This is called “autoactivation”.

The D816V mutation is one of the minor criteria for systemic mastocytosis, so it is important for classification purposes. Also, it may affect your treatment plan in the unlikely situation of needing chemotherapy.


What is CD25?

CD25 is part of a receptor for a molecule called IL-2. Normally, mast cells do not express receptors for IL-2, which is a molecule that regulates development of T cells. When mast cells express CD25, it is an indication that the mast cell is neoplastic. Many T cells normally express CD25, so if it is on a biopsy report, keep in mind that it’s abnormal on mast cells, but not everywhere.

Presence of CD25 on mast cells is one of the minor criteria for SM.


What is CD2?

CD2 is an example of a “CD” molecule that is not a receptor. It is a cell adhesion molecule so it helps cells stick together. Normally, mast cells do not express CD2. When mast cells express CD2, it is an indication that the mast cell is neoplastic. Many T cells normally express CD25, so if it is on a biopsy report, keep in mind that it’s abnormal on mast cells, but not everywhere. CD2 is a less accurate indication of SM than CD25.

Presence of CD2 on mast cells is one of the minor criteria for SM.


What is CD30?

CD30 is a receptor for proteins associated with tumor necrosis factor. It is commonly referred to as a tumor marker, but this is not always the case. CD30 has recently been shown to be frequently positive in patients with all forms of SM (ISM, SSM, SM-AHNMD, ASM). However, on other cells besides mast cells, it may indicate lymphoma or other conditions.


What is CD34?

CD34 is another cell adhesion molecule. It is thought to allow stem cells to attach to proteins in the bone marrow. It is found on many progenitor cells, cells that later become other kinds of cells. Mast cells express CD34, though this tends to be lost as they move into tissues.

What do all these words mean? (Part 1)

What is a neoplasm?

A neoplasm is an abnormal growth of cells. Systemic mastocytosis is a neoplasm because your body makes too many mast cells. Cancers are all neoplasms, but not all neoplasms are cancers. SM is not cancer.


What is a myeloproliferative neoplasm (MPN)?

Myelo- means “related to granulocytes”, cells that store chemicals in granules. Mast cells are a type of granulocyte.

Proliferative means “cell growth”.

So together you have “growth of too many granulocytes”.


What are receptors?

Receptors are proteins on the outside of cells. They have very unique and specific shapes, but it is easier to think of them as being shaped by cups. Only very specific molecules fit into these cups. When the molecule is in the receptor, the cell knows to do something. What this something is varies a lot from receptor to receptor.

For example, when an IgE antibody binds to the IgE receptor on a mast cell, the mast cell degranulates. However, not any molecule would be able to bind in the IgE receptor and cause this action.


What are antibodies?

These are large proteins that help the immune system identify and destroy things like bacteria and viruses. Sometimes your body mistakenly makes antibodies to things inside the body. This causes autoimmune disease.

In labs, antibodies are very useful. There are ways to make antibodies to almost anything in the lab. Using these lab made antibodies, scientists are able to test for specific structures that tell us what cells are present in a sample and how the cells are working.


What are immunoglobulins?

They are the same as antibodies.


What does CD mean? Like in CD117?

CD means “cluster of differentiation”. This means that it is a protein or group of proteins on the surface of a cell that is recognized by an antibody. This means that in a lab, if I use an antibody called “ABC123” and it binds to a specific protein on the outside of cells, that protein will be called “CD-ABC123”.

Over time, as we learn more about “CD-ABC123”, we may realize that this protein is made by a gene called “Wow”. So some people will call it “Wow” and some will continue to call it “CD-ABC123”, which can be confusing. Generally speaking, scientists who work with antibody testing usually use the “CD-ABC123” name and doctors use the “Wow” name. However, both names are still correct.

Receptors are often given “CD” names, but not all “CD” molecules are receptors. Some “CD” molecules are on the outside of cells to do other things, like help cells stick to other cells.


What is CKIT?

CKIT is a receptor that is found on all mast cells, whether or not a person has mast cell disease. The CKIT receptor is also called CD117. They are the same thing. CKIT is sometimes also called KIT. They are also the same thing.

The molecule that fits in the CKIT receptor is called stem cell factor (SCF). When SCF binds the CKIT receptor, it tells the mast cell to stay alive much longer than it is supposed to. It also starts a process that tells mast cells to make more mast cells.


CKIT (CD117) is only found on mast cells?

No, other normal cells have CKIT (CD117) on their surface. Epithelial cells in the skin, breast and some parts of the brain express CD117. Some stem cells in the bone marrow and melanocytes also express CD117. Smooth muscle and fibroblasts do not express CD117. This is important because smooth muscle and fibroblasts are often found close to the cells we might be looking for that may be positive for CD117.

However, when found on cells that don’t normally express CD117, it can be a sign of cancer – but ONLY if these cell types don’t normally have CD117 on their surfaces. Examples of cancers that express CD117 include angiosarcoma and Ewing sarcoma.

Mast cells in vascular disease: Part 1

Atherosclerosis is a very specific type of artery hardening that occurs due to accumulation of white blood cells and their inflammation of the vessel. Atherosclerosis can cause heart attacks, formation of blood clots and obstruction of major vessels. There are a number of risk factors, including tobacco smoking, high LDL cholesterol, diabetes, vitamin B6 deficiency, high C reactive protein, and many others.

Atherosclerosis is now known to be an immunoinflammatory condition, one which results from inflammation mediated by immune cells. In recent years, mast cells have been found to play an important role in the formation of atherosclerotic lesions, progression and destabilization of the lesion, which in turn causes the more significant clinical effects. In 2004, 66% of men and 47% of women in the US had heart attack or sudden cardiac death as their first symptom of atherosclerotic heart disease.

Endothelial cells line the blood vessels and form the endothelium. In atherosclerotic plaques, monocytes from the blood burrow into the endothelium. They turn into macrophages, a different kind of cell. These macrophages eat certain kinds of cholesterol and start a cycle in inflammation in the vessel wall. Platelets then stick to the inflamed places.

Mast cells are known to have a number of behaviors that affect plaque pathology. Mast cells near plaques release tryptase, which activates endothelial cells through the PAR-2 receptor. This causes a series of events that produces platelet activating factor (PAF). PAF increases the permeability and contraction of the nearby smooth muscle, which can lead to vascular events.

Increased densities of mast cells have been found in the tissue layer overlaying plaques that ruptured. It has been hypothesized that mast cell released histamine could cause coronary spasm, making the plaque more likely to rupture. In a study that looked at 44 autopsy samples of aorta with atherosclerotic lesions, there was a direct correlation found between levels of tryptase and chymase, the amount of collagen in the plaque, and the size of the endothelium involved.

Mast cells that store basic fibroblast growth factor (bFGF) are found in small vessels inside plaques. Histamine may cause leakage from those tiny vessels, which can further make the plaque more likely to rupture.   In histamine deficient mice, the plaque area was reduced in size, and expression of genes for NF-kB, matrix metalloproteinases (MMPs), and inflammatory cytokines involved in plaque progression. Histamine is also involved in acute coronary vasospasm that may result in heart attack; this is called Kounis Syndrome.



Simon Kennedy, Junxi Wu, Roger M. Wadsworth, Catherine E. Lawrence, Pasquale Maffia. Mast cells and vascular diseases. Pharmacology & Therapeutics 138 (2013) 53–65.

Ramalho, L. S., Oliveira, L. F., Cavellani, C. L., Ferraz, M. L., de Oliveira, F. A., Miranda Corrêa, R. R., et al. (2012). Role of mast cell chymase and tryptase in the progression of atherosclerosis: study in 44 autopsied cases. Ann Diagn Pathol 17, 28–31.

Lappalainen,H., Laine, P., Pentikäinen,M. O., Sajantila,A.,& Kovanen, P. T. (2004).Mast cells in neovascularized human coronary plaques store and secrete basic fibroblast growth factor, a potent angiogenic mediator. Arterioscler Thromb Vasc Biol 24, 1880–1885.

Kounis, N. G., Mazarakis, A., Tsigkas, G., Giannopoulos, S., & Goudevenos, J. (2011). Kounis syndrome: a new twist on an old disease. Future Cardiol 7, 805–824.

Effects of Platelet Activating Factor (PAF) in asthma and anaphylaxis

PAF is released by many different cells, including eosinophils, mast cells, neutrophils, monocytes, macrophages and endothelial cells. PAF receptors are expressed by platelets, monocytes, mast cells, neutrophils, and eosinophils. T and B cells do not express PAF receptors, but PAF can stimulate them to migration of these cells. PAF receptors are found to be increased in eosinophils of asthma patients. PAF receptors are also elevated in lungs of asthmatic patients. PAF can activate mast cells and basophils, causing histamine release. One study proposed the PAF activation of basophils may play a role in aspirin sensitivity in asthma patients.

PAF is most well known for its effects on the airway. It causes constriction of the airway and can affect the way oxygen is brought into the lungs. However, it also has many other effects in the body, many of which affect anaphylaxis and severity thereof.

PAF activates eosinophils and neutrophils to degranulate. It also causes leukotriene C4 production by activated eosinophils in asthma patients, but not in normal patients. A PAF inhibitor has been observed to prevent eosinophil migration and leukotriene C4. Another PAF inhibitor was able to inhibit eosinophil activation by PAF. In activated neutrophils in asthma patients, PAF causes an increase in secretion of leukotriene B4 and increased 5-lipoxygenase activity.

PAF is a powerful signal for eosinophils to migrate toward the cell releasing PAF, and may be involved in inflammation resulting in eosinophilic infiltration. PAF can cause eosinophilic movement across endothelium and into airway. This behavior is increased during asthma attacks and can be minimized with steroids.

PAF injected into the skin causes a biphasic reaction with immediate hiving, then a delayed redness and pain reaction that causes eosinophilic infiltration. PAF also increases IL-6 production by macrophages, activates IL-4 production by T cells, and enhances IL-6 production by mononuclear cells in peripheral blood.

PAF has been heavily linked to asthma. One study found higher levels of PAF as well as lower level of the enzyme that inactivates PAF in plasma of asthmatic adults both during attacks and the rest of the time. When exposed to allergens, PAF level in blood rapidly increases. The large increases in PAF level upon exposure were ameliorated upon successful allergen immunotherapy (also known in the US as “allergy shots”).

PAF induced bronchoconstriction does not affect histamine release and is not alleviated by H1 receptor antihistamines. Inhaling PAF does not change plasma histamine level in asthmatics. Leukotrienes may behave as secondary mediators of PAF action. Zileuton attenuated systemic and respiratory effects of PAF, including airway constriction and changes in neutrophil behavior.

PAF level, and the level of the enzyme that metabolizes it, PAF-acetylhydrolase, is directly correlated to severity of anaphylaxis. Patients with grade I anaphylaxis have 2.5x as much PAF as controls; grade II, 5x; and grade III, 10x. PAF blockers are being investigated for use in this context. Rupatadine is available in some countries, and has H1 antihistamine and PAF blocking activity.

The exact nature of PAF’s activity in anaphylaxis is unclear. It has been shown to cause mast cell degranulation and increased production and release of prostaglandin D2. It can also amplify the response to IgE, making the allergic reaction worse. However, these effects were not seen in skin mast cells for unknown reasons. The source of PAF that acts on mast cells in anaphylaxis is unknown, but is thought to be at least partially from mast cells themselves.



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