mast cell activation

Definition

Target type: biologicalprocess

The change in morphology and behavior of a mast cell resulting from exposure to a cytokine, chemokine, soluble factor, or to (at least in mammals) an antigen which the mast cell has specifically bound via IgE bound to Fc-epsilonRI receptors. [GOC:mgi_curators, ISBN:0781735149]

Mast cell activation is a complex process that involves the recognition of specific stimuli by receptors on the surface of mast cells, followed by a cascade of intracellular signaling events that ultimately lead to the release of a variety of potent mediators. These mediators can contribute to a wide range of physiological and pathological processes, including inflammation, allergy, and immunity.

**Stimuli that Trigger Mast Cell Activation**

Mast cells are highly sensitive to a variety of stimuli, including:

- **Immunoglobulin E (IgE):** IgE is an antibody that is produced by B cells and binds to FcεRI receptors on the surface of mast cells. When IgE binds to its receptor and is subsequently cross-linked by an allergen, this triggers the release of mast cell mediators. This is the mechanism involved in allergic reactions.

- **Complement proteins:** Certain complement proteins, such as C5a, can directly activate mast cells.

- **Cytokines:** Interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), and other cytokines can also activate mast cells.

- **Physical stimuli:** Mechanical injury, heat, and cold can also trigger mast cell activation.

- **Neurotransmitters:** Neurotransmitters such as substance P can stimulate mast cell activation.

**Intracellular Signaling Pathways**

Once a stimulus is recognized, it initiates a series of intracellular signaling events. These events involve:

- **Tyrosine kinase signaling:** The FcεRI receptor, upon cross-linking, triggers the activation of tyrosine kinases such as Lyn and Syk.

- **Calcium signaling:** Tyrosine kinases activate phospholipase Cγ (PLCγ), which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 increases intracellular calcium levels, which triggers the release of preformed mediators from granules.

- **Activation of transcription factors:** DAG activates protein kinase C (PKC), which in turn phosphorylates and activates transcription factors such as nuclear factor κB (NF-κB) and activator protein-1 (AP-1). These transcription factors regulate the expression of genes encoding for newly synthesized mediators.

**Mediators Released by Mast Cells**

Mast cells release a wide range of mediators, including:

- **Preformed mediators:**
- **Histamine:** A potent vasodilator and bronchoconstrictor.
- **Heparin:** An anticoagulant.
- **Proteases:** Enzymes that degrade proteins.
- **Chemotactic factors:** Molecules that attract other immune cells to the site of inflammation.

- **Newly synthesized mediators:**
- **Leukotrienes:** Proinflammatory lipid mediators that cause bronchoconstriction and smooth muscle contraction.
- **Prostaglandins:** Lipid mediators that contribute to inflammation and pain.
- **Cytokines:** Signaling molecules that regulate immune responses.

**Functions of Mast Cell Activation**

Mast cell activation plays a crucial role in:

- **Immune defense:** Mast cells participate in the innate immune response against parasites and bacterial infections.

- **Inflammation:** Mast cell mediators contribute to the development of inflammatory responses.

- **Allergy:** Mast cell activation is the key event in allergic reactions, leading to symptoms such as sneezing, runny nose, and difficulty breathing.

- **Wound healing:** Mast cells promote wound healing by releasing growth factors and other mediators.

- **Tissue remodeling:** Mast cells contribute to tissue remodeling in response to injury or infection.

**Dysregulation of Mast Cell Activation**

Excessive or inappropriate mast cell activation can contribute to a variety of pathological conditions, including:

- **Allergic diseases:** Asthma, hay fever, and food allergies.

- **Autoimmune diseases:** Rheumatoid arthritis, systemic lupus erythematosus.

- **Inflammatory bowel disease:** Crohn's disease, ulcerative colitis.

- **Chronic urticaria:** A skin condition characterized by itchy welts.

- **Mastocytosis:** A rare condition characterized by an overgrowth of mast cells.

**Conclusion**

Mast cell activation is a highly regulated process that plays a critical role in both health and disease. Understanding the mechanisms of mast cell activation is essential for developing new therapeutic strategies for a wide range of conditions.'
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Compounds (23)