Mast cell degranulation
The moment a mast cell empties its storage vesicles and releases histamine and other inflammatory substances into its surroundings. This can be triggered by an allergen, but also by medication, heat, or stress.
Mast cells store histamine in small vesicles called granules. Along with histamine, they contain tryptase, heparin, and other inflammatory mediators. Degranulation is the exact moment when the cell dumps the contents of these vesicles all at once. Within a few minutes, such a large amount of histamine appears in the tissue that the body cannot keep up with breaking it down.
This process can be triggered through two different pathways, and distinguishing between them is crucial for histamine intolerance.
The first is the allergic pathway. Here, the body must already recognize the substance and have formed specific antibodies against it. This is a classic allergy that can be measured via standard testing.
The second is the non-allergic pathway, which requires no antibodies. A given substance or stimulus irritates the cell directly. A key role here is played by a receptor named MRGPRX2 (discovered only recently) which is found specifically on mast cells and responds to a wide variety of substances, including common medications. This category includes histamine liberators in food, certain drugs like morphine, vancomycin, contrast agents, or some painkillers, as well as alcohol, cold, heat, pressure on the skin, physical exertion, and psychological stress.
This explains a situation that confuses many people: a person reacts to a food for which no allergy test showed a positive result. It is not that the test was wrong; the reaction was simply triggered through a different pathway. This is why, in histamine intolerance, it pays to monitor triggers that have nothing to do with food as well.
Excessive and easily triggered degranulation is also the core underlying mechanism of Mast Cell Activation Syndrome (MCAS), which is frequently confused with histamine intolerance.
Related terms
Immune system cells that release histamine and other mediators in response to HIT triggers.
A build-up of histamine in the body from various sources that exceeds tolerance and triggers symptoms.
The process by which microorganisms convert substances. It is key in HIT because it increases the histamine content of food.
Medications that prevent histamine from binding to receptors. However, they do not break histamine down; they only blunt its effect. In this way, they differ from DAO supplementation.
An independent non-profit organization (Schweizerische Interessengemeinschaft Histamin-Intoleranz) that specializes in research, education and support for people suffering from histamine intolerance (HIT) and related disorders of mast cell metabolism.