Clinically significant causes of mast cell activation

There are many things that can trigger significant mast cell activation and degranulation.  The ones most well defined are allergens, which trigger degranulation by the binding of an allergen specific IgE molecule to the mast cell IgE receptor.  However, there are lots of others.

The anti-IgE IgG antibody is an antibody made by your body that incorrectly thinks that the IgE molecule should be targeted.  High levels of this antibody are found in patients with chronic autoimmune urticarial.  Sometimes, these patients may have elevated levels of anti-FceRI, an antibody that targets te a receptor on the mast cell.  Both of these antibodies can cause mast cell activation.

Several components can activate mast cells due to their mutual function in immune defense.  IgG is an antibody subtype that protects the body from infection.  As mast cells are involved in defending the body from dangerous organisms, IgG is able to bind to mast cells and cause activation.  So IgG can also cause mast cell degranulation.

Complement peptides, including C3 and C5a, are produced to help your body clear dangerous infecting organisms.  These molecules cause smooth muscle contraction and histamine release from mast cells.  They are also known as anaphylatoxins.  There are also several bacterial products that cause mast cell activation, including peptidoglycan and lipopolysaccharide.  For these reasons, infections can be dangerous for mast cell patients.

Lots of cell signaling molecules called cytokines can activate mast cells.  They have a wide array of functions and some of them are known to activate mast cells, like stem cell factor, nerve growth factor and macrophage inflammatory protein 1 alpha.  Please keep in mind that cytokines compose a large, diverse group of molecules with  many functions, and includes things like interferon, which is used to treat advanced mast cell disease.

Another type of signaling molecule, the neuropeptide, can also be triggering.  Neuropeptides are small molecules that nerve cells use to talk to each other.  These include molecules like norepinephrine, acetylcholine, serotonin and others.  Concentrations of these molecules can influence mast cell activation.

Medications can be hugely activating.  A general list of medications to avoid (unless non-reactive or desensitized) includes: aspirin; non-steroidal anti-inflammatories; decamethonium; opiates (this in particular varies from person to person – fentanyl and hydromorphone generally cause the least histamine release); iodine-containing contrast; scopolamine; gallium; quinine; polymyxin B; amphotericin; tubocurarine; reserpine; colistin; dipyridamole; dextromethorphan; stilbamadine; chlortetracycline; hydrazaline; tolazoline; amphetamines; amino amides (like lidocaine); vancomycin; adenosine; and antifungals. 

Heat, cold and pressure can all cause direct mast cell activation.  Extremes of all three should be avoided.  Hormones, including estrogen, progesterone, alpha melanocyte stimulating hormone and chorionic somatomammotropin hormone can all also directly activate mast cells.

Neoplastic activity in the body, either due to a non-malignant neoplasm or cancer, causes generation of complement proteins and cytokines.  For this reason, and others, they can induce mast cell degranulation.  It is for this reason that mast cell mediator release symptoms (sometimes referred to as MCA – mast cell activation) are considered an inherent part of SM, which is caused by a neoplasm.