Mast cells are immune cells mostly concentrated in the tissues that meet the outside world: your skin, gut lining and airways. Here they stand guard, watching for invaders. When activated, they release a burst of chemical messengers. These messengers are called mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. mediators.
If you live with systemic mastocytosis (SM), these mediators matter because they drive both your symptoms and many of the tests and treatments you will encounter.
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What are mast cell mediators?
Mediators are the chemicals a mast cell stores or produces and then releases when it is activated. Researchers have so far cataloged at least 390 different mediators in human mast cells.
In plain terms, a single cell type can affect the body in many ways.
They fall into two broad groups:
- Pre-formed mediators: These mediators are stored in granules and released within seconds. This group includes histamine and tryptase.
- Newly made mediators: These mediators are built only after the cell is activated. This group includes prostaglandins, leukotrienes and signaling proteins called cytokines.
Tumor necrosis factor-α (TNF-α), an inflammatory cytokine, belongs to both groups.
Why this matters for your care
In SM, the body makes too many mast cells, and they release their mediators too readily. If you live with SM, most of your symptoms trace back to what gets released.
Where mast cells build up in your body and the particular mix of mediators they release shape which symptoms you experience, and can affect which treatments are most helpful. Keeping a simple record of your symptoms and possible triggers gives your specialist something concrete to work from when developing your treatment plan.
Key mast cell mediators to know
Histamine
Histamine causes flushing, itching, hives, increased stomach acid and a drop in blood pressure. It drives many of the allergy-type symptoms in mastocytosisMastocytosis Rare disease caused by the buildup of mast cells. Cutaneous mastocytosis primarily affects the skin and is more common in children, while systemic mastocytosis affects internal organs and is more common in adults., which is why antihistaminesAntihistamines Medications that block the effects of histamine, the chemical found in mast cells that is responsible for many of the symptoms of SM, as well as many allergic reactions. are a common first-line treatment.
Tryptase
TryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM. is the most abundant protein stored in mast cell granules. Its precise role is still not fully understood, but it contributes to inflammation and affects the airways, blood vessels, gut muscle activity and blood clotting.
Prostaglandin D2
Made fresh upon mast cell activationMast cell activation Describes when mast cells release histamine and other mediators into the blood stream in response to an allergen or other trigger. This leads to symptoms like fatigue, rash and, in severe cases, anaphylaxis., prostaglandin D2 contributes to flushing, airway narrowing and lightheadedness. Mast cells are its main source in the body, and aspirin-type drugs (NSAIDs) lower it — one reason your care team may ask about NSAID use.
Leukotrienes
These lipid mediators tighten the airways and increase mucus and swelling. Leukotriene-blocking medicines used in asthma are sometimes used to help manage mastocytosis symptoms for the same reason.
Read more about SM signs and symptoms
How these mediators are measured
Some mediators leave measurable traces that can be used to confirm mast cell activity and track it over time.
Blood sample
Tryptase is checked in a blood sample. Your baseline level broadly reflects your mast cell load, so a persistently raised reading is one of the factors doctors weigh when diagnosing SM: a sharp rise above your usual level during symptoms points to an episode of mast cell activation.
Urine sample
Breakdown products of histamineHistamine A chemical released by mast cells when they are activated. Histamine causes many of the allergy-type symptoms in mastocytosis, including flushing, itching and hives., leukotrienes, and prostaglandin D2 can be measured in urine. These help show whether mast cells are active, but they are not part of the criteria used to diagnose SM itself.
