The Role of Mast Cells in Health and Disease: Part 1

A Primer on Mast Cell Biology

Jul 30, 2023

Mast cells are immune cells that originate from the bone marrow. Mast cells contain large granules with mediators inside that can be released upon their activation. Mast cells can be found in the connective tissues throughout the body and have multifaceted functions in normal physiological processes and human disease. Initially, mast cells were believed only to play a role in allergic reactions; however, we are beginning to understand that they play a much bigger role beyond this.

A transmission electron micrograph of a mast cell showing granules of mediators.

Mast Cells In Normal Physiological Processes

Mast cells date back more than 500 million years and are present in all vertebrates. The evolutionary preservation of mast cells suggests that they may have important roles in human life beyond our current understanding.

Based on our current understanding of mast cells, we know that they are important in wound healing, responding to pathogens, the growth of new blood vessels (angiogenesis), tissue re-modeling, gastrointestinal functions, female reproduction, and more.

An example of the role of mast cells in dermal scarring. From Wilgus TA, Wulff BC. The Importance of Mast Cells in Dermal Scarring. Advances in Wound Care 2014 3:4, 356-365.

Activation and Degranulation

Mast cell degranulation is the process by which mast cells become activated and release their granules containing various mediators into the surrounding tissues. Degranulation can be triggered by different stimuli, including allergens, mechanical stimuli, temperature, infections, hormones, and chemical exposure. One well-understood example of mast cell activation is IgE-Mediated Allergic Reactions, outlined below.

Sensitization: Exposure to an allergen triggers the production of specific IgE antibodies.
IgE Attachment: IgE antibodies attach to mast cells, sensitizing them to the allergen.
Re-Exposure: Upon re-exposure to the allergen, it binds to the IgE antibodies on mast cells.
Degranulation: Cross-linking of IgE receptors on mast cells leads to degranulation.
Mediator Release: Mast cells release inflammatory mediators, such as histamine and cytokines.
Inflammatory Response: Released mediators cause allergy symptoms like itching, hives, and congestion.

IgE cross-linking is only one mechanism of mast cell activation and degranulation.

Mediators and Receptors

Mast cell mediators released during degranulation can include proteases such as chymase and tryptase, histamine, cytokines and chemokines, growth factors, and more. These mediators regulate downstream processes and physiological responses.

Mast Cell Mediators. From: Wilgus, T.A.; Ud-Din, S.; Bayat, A. A Review of the Evidence for and against a Role for Mast Cells in Cutaneous Scarring and Fibrosis. Int. J. Mol. Sci. 2020, 21, 9673. https://doi.org/10.3390/ijms21249673

Mast cells possess various receptors on their surface, which enable them to detect and respond to different stimuli. Some of their receptors include:

IgE Receptors (FcεRI): These receptors bind to IgE antibodies.

Complement Receptors: Interact with components of the complement system, which is part of the innate immune response.

Pattern Recognition Receptors (PRRs): Allow mast cells to recognize pathogens.

Neuropeptide Receptors: Allow interaction with sensory nerves

Cytokine Receptors: Receptors for immune signaling molecules.

Chemokine Receptors: Receptors that allow for chemokines to interact with mast cells, small proteins that guide immune cells to specific locations in the body.

Histamine Receptors: While mast cells release histamine during degranulation, they also express histamine receptors on their surface

Types of Mast Cells

Mast cells can be found in connective tissues throughout the body, particularly near blood vessels and nerve endings. They are especially prevalent in areas where the body interacts with the external environment, such as the skin, respiratory tract, and gastrointestinal tract. There are two types of mast cells in humans: mucosal mast cells and connective tissue mast cells, which differ in their location and mediators.

Mucosal Mast Cells: Express tryptase, found primarily in the GI mucosa and peripheral airways

Connective Tissue Mast Cells: Express tryptase and chymase, found primarily in loose connective tissue and skin

Key Takeaway

Mast cells can be highly sensitive immune cells that respond to a range of stimuli and can have a variety of downstream consequences from their degranulation depending on the mechanism of activation, meditators released, location of the cell, and disease state. Our understanding of mast cell biology is still fairly new. This field is growing and changing constantly!

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