mast cell apoptotic process

Definition

Target type: biologicalprocess

Any apoptotic process in a mast cell, a cell that is found in almost all tissues containing numerous basophilic granules and capable of releasing large amounts of histamine and heparin upon activation. [CL:0000097, GOC:add, GOC:mtg_apoptosis, PMID:11292031, PMID:12360215, PMID:16605130]

Mast cell apoptosis is a tightly regulated process that plays a critical role in maintaining tissue homeostasis and preventing excessive inflammation. It involves a cascade of molecular events leading to the programmed death of mast cells, characterized by distinct morphological and biochemical changes.

The initiation of mast cell apoptosis can be triggered by a variety of stimuli, including:

* **Extrinsic pathways:** These pathways are activated by external signals, such as engagement of death receptors on the cell surface. Examples include Fas ligand (FasL), tumor necrosis factor-alpha (TNF-α), and TRAIL (TNF-related apoptosis-inducing ligand). These ligands bind to their respective death receptors, triggering the formation of the death-inducing signaling complex (DISC). The DISC recruits caspase-8, an initiator caspase, which activates the caspase cascade, leading to apoptosis.
* **Intrinsic pathways:** These pathways are activated by internal stress signals, such as DNA damage, oxidative stress, and ER stress. These stressors activate the mitochondria, leading to the release of cytochrome c into the cytoplasm. Cytochrome c binds to apoptotic protease activating factor 1 (Apaf-1), forming the apoptosome. The apoptosome activates caspase-9, another initiator caspase, triggering the caspase cascade.

**Caspase cascade:** The caspase cascade is a central event in apoptosis. Initiator caspases, such as caspase-8 and caspase-9, activate effector caspases, such as caspase-3, caspase-6, and caspase-7. These effector caspases cleave various cellular substrates, leading to the characteristic morphological and biochemical changes of apoptosis.

**Morphological changes:** Apoptosis is characterized by several distinct morphological changes, including:

* **Cell shrinkage:** The cell shrinks and becomes more dense.
* **Nuclear fragmentation:** The nucleus condenses and fragments into apoptotic bodies.
* **Plasma membrane blebbing:** The plasma membrane forms blebs or bulges.
* **Apoptotic bodies:** The cell fragments into membrane-bound vesicles called apoptotic bodies.

**Biochemical changes:** Apoptosis also involves several biochemical changes, including:

* **DNA fragmentation:** The DNA is cleaved by caspase-activated DNase (CAD) into fragments of 180-200 base pairs.
* **Phosphatidylserine exposure:** Phosphatidylserine, a phospholipid normally confined to the inner leaflet of the plasma membrane, translocates to the outer leaflet, where it acts as a signal for phagocytosis.
* **Cytokine release:** Mast cells release cytokines, such as TNF-α and IL-10, which contribute to the inflammatory response.

**Phagocytosis:** Apoptotic bodies are engulfed and digested by phagocytes, preventing the release of cellular contents and inflammation.

**Dysregulation of mast cell apoptosis:** Aberrant mast cell apoptosis can contribute to various pathological conditions, including:

* **Allergic diseases:** Increased mast cell survival and decreased apoptosis contribute to the development of allergic diseases, such as asthma and allergic rhinitis.
* **Autoimmune diseases:** Mast cell dysfunction, including impaired apoptosis, can contribute to autoimmune diseases, such as systemic lupus erythematosus.
* **Cancer:** Mast cells can contribute to tumor growth and metastasis by releasing pro-angiogenic and pro-inflammatory mediators.

**Therapeutic implications:** Modulation of mast cell apoptosis holds promise for the treatment of various diseases. For example, targeting the caspase cascade could prevent unwanted mast cell apoptosis in allergic diseases, while promoting mast cell apoptosis could be beneficial in treating cancer.

**Conclusion:** Mast cell apoptosis is a complex and tightly regulated process that is essential for maintaining tissue homeostasis and preventing inflammation. Dysregulation of mast cell apoptosis can contribute to various pathological conditions, and targeting mast cell apoptosis pathways holds promise for the development of novel therapies.'
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Compounds (2)