mast cell degranulation

Definition

Target type: biologicalprocess

The regulated exocytosis of secretory granules containing preformed mediators such as histamine, serotonin, and neutral proteases by a mast cell. [ISBN:0781735149]

Mast cell degranulation is a crucial process in the body's immune response, particularly in allergic reactions and inflammation. It involves the rapid release of pre-formed mediators from mast cell granules into the surrounding environment. Here's a detailed breakdown of the process:

1. **Activation:** Mast cells are activated by various stimuli, including:
* **Allergens:** These are substances like pollen, dust mites, or certain foods that trigger an immune response in individuals with allergies. They bind to IgE antibodies attached to the surface of mast cells, triggering a cascade of signaling events.
* **Other Immune Signals:** Cytokines, chemokines, and complement proteins released during immune responses can also activate mast cells.
* **Physical Stimuli:** Direct physical injury, heat, or cold can also lead to mast cell degranulation.

2. **Signaling Cascade:** Upon activation, mast cells initiate a complex signaling cascade that involves:
* **Cross-linking of IgE:** Allergens bind to multiple IgE antibodies attached to the cell surface, causing their aggregation.
* **Activation of tyrosine kinases:** This aggregation triggers the phosphorylation of tyrosine residues in intracellular proteins, including Syk, a key enzyme in mast cell signaling.
* **Activation of downstream pathways:** Syk initiates a series of downstream pathways involving PLCγ, DAG, IP3, and Ca2+ influx.

3. **Calcium Influx:** The activation of these pathways leads to increased intracellular calcium levels. This is crucial for triggering degranulation.

4. **Exocytosis:** Elevated calcium levels promote the fusion of mast cell granules with the plasma membrane. This process, known as exocytosis, releases the pre-formed mediators stored within the granules into the extracellular space.

5. **Mediator Release:** These mediators include:
* **Histamine:** A potent vasoactive amine that causes vasodilation, increased vascular permeability, and bronchoconstriction.
* **Tryptase:** A serine protease that can activate other immune cells and contribute to inflammation.
* **Chymase:** Another serine protease involved in tissue remodeling and inflammation.
* **Heparin:** An anticoagulant that inhibits blood clotting.
* **Cytokines and Chemokines:** These signaling molecules attract other immune cells to the site of inflammation and contribute to the inflammatory response.

6. **Effects of Mediator Release:** The released mediators contribute to the characteristic symptoms of allergic reactions and inflammation:
* **Vasodilation and Increased Permeability:** Leads to swelling, redness, and fluid leakage.
* **Bronchoconstriction:** Causes airway narrowing and difficulty breathing.
* **Inflammation:** Recruits other immune cells, promoting the inflammatory response.

7. **Regulation of Degranulation:** Several mechanisms exist to regulate mast cell degranulation and prevent excessive inflammation:
* **Negative Feedback Loops:** The released mediators themselves can activate negative feedback loops, limiting further degranulation.
* **Immune Tolerance:** Repeated exposure to allergens can lead to immune tolerance, decreasing mast cell sensitivity.
* **Anti-inflammatory Drugs:** Medications like antihistamines and corticosteroids can block or suppress mast cell degranulation and reduce inflammation.

In summary, mast cell degranulation is a complex process involving a cascade of signaling events, calcium influx, and exocytosis, leading to the release of various mediators that contribute to the development of allergic reactions and inflammation. Understanding this process is crucial for developing effective therapies for allergic diseases and other inflammatory conditions.'
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Proteins (10)

Compounds (513)