Introduction to mast cells and MCAS

Hey everyone, it’s Sam again! I reached out to you guys via the Facebook community a few weeks ago and got a few requests for information on mast cells and MCAS. I personally don’t have MCAS, so it’s not something I research as intently, but I LOVE immunology and thought this would be a really fun thing to talk about.

Immunology can be a scary subject, even for biologists. It’s very detail-oriented, there are a LOT of things going on, and the scientific community still doesn’t understand a lot about how the players in the immune system work. We do know that the immune system interacts with other parts of the body, like the nervous system (neuroimmunology recently crossed my radar and I’m enthralled!), to cause some interesting effects, so immunology is becoming a hotter and hotter topic for research.

The big player in MCAS is, as the name implies, the mast cell. To understand MCAS, we need to break down what mast cells are and what they do.

These guys are mast cells:

They have a bunch of receptors on their cell surface that let them talk to other cells in the body and receive input from both other cells and the environment they’re in. All those dark purple circles you see in the image above are called granules. Many different cell types have granules in them, and they can hold different types of chemicals (often called cytokines or chemokines) depending on what the cell needs to do. Mast cells usually have granules full of histamine, but they can also hold enzymes that chop up proteins (proteases), neurotransmitters like serotonin, and a bunch of other types of chemical messengers and enzymes. Histamine is the compound we usually talk about when discussing mast cells and allergy, and it makes a lot of different things happen depending on where it’s released.

So….what exactly does histamine do? There are 4 main histamine receptors in the body, and when they’re activated, each one can cause different things to happen. Some are more common in different parts of the body, which is why histamine can trigger different kinds of reactions. From typical seasonal allergy-type reactions or skin irritation to GI symptoms, to nervous system effects like nausea and vertigo, and even anaphylaxis, histamine can trigger a wide range of symptoms which is why MCAS can be difficult to diagnose. Many signs can be relatively benign or nonspecific, but when typical allergy testing comes up negative, it may be time to investigate MCAS.

Keep in mind that the other chemicals mast cells release can cause other things to happen, too. It’s not all about histamine!

So how are mast cells activated? Mast cells have cell surface receptors that can bind allergens, specific classes of antibodies, and signals sent out by other immune cells. When activated, mast cells release their granules, which then break open and release their contents into the local environment and trigger other events to happen.

It isn’t fully understood why mast cells don’t behave normally in MCAS. It’s important to note that MCAS is not the same as mastocytosis, which is characterized by an abnormally high number of mast cells; in mast cell activation syndrome, mast cells are activated too easily and are releasing their contents in situations they typically wouldn’t. Some environmental triggers can stimulate mast cells, like excessive heat or cold, sunlight, mechanical irritation, and chemicals or products on skin. There’s an observed correlation between MCAS, POTS, and EDS that isn’t fully understood.

MCAS is a very involved disorder, and it would take significantly more than just one post to do it justice. Hopefully this quick overview was helpful! Don’t hesitate to reach out to me via the EDS, Wisconsin Inc. contact page, or on the EDS & Joint Hypermobility Wisconsin Facebook page if you have anything in particular you’d like for me to discuss in detail.

*Disclaimer: I am not a physician, and I am not qualified to give anyone advice about their medical condition. All posts written by me are strictly meant to inform and empower patients and medical professionals alike, with the information they can use to better communicate with each other. If you have questions about your condition, please ask your doctor.

Citations:

• Mast cell secretory granules: armed for battle. Wernersson S, Pejler G. 2014. Nature Reviews Immunology. 14: 478-494.
• Mast cell activation syndrome: a review. Frieri M, Patel R, Celestin J. 2012. Current Allergy and Asthma Reports. 13(1): 27-32.
• https://tmsforacure.org
• http://www.mastcellaware.com
• Mast cell activation syndromes. Akin C. 2017. Allergy and Clinical Immunology. 140(2): 349-355.
• Misbehaving Mast Cells in POTS and Other Forms of Dysautonomia – https://vimeo.com/246313546 (I didn’t actually watch this, but thought it would be a great resource!)