leukocyte apoptotic process

Definition

Target type: biologicalprocess

Any apoptotic process in a leukocyte, an achromatic cell of the myeloid or lymphoid lineages capable of ameboid movement, found in blood or other tissue. [CL:0000738, GOC:BHF, GOC:mah, GOC:mtg_apoptosis]

Leukocyte apoptosis is a tightly regulated process essential for maintaining immune homeostasis and preventing uncontrolled inflammation. It involves a cascade of molecular events leading to the dismantling of the cell, ultimately resulting in its engulfment by phagocytes.

1. **Initiation:** The apoptotic cascade can be triggered by various stimuli, including:
* **Extrinsic pathway:** Activation of death receptors (e.g., TNF receptor, Fas) on the leukocyte surface by ligands expressed by other cells or pathogens. This leads to the recruitment of adaptor proteins and activation of caspase-8, initiating the caspase cascade.
* **Intrinsic pathway:** Internal stress signals like DNA damage, oxidative stress, or growth factor deprivation activate the mitochondria to release pro-apoptotic proteins like cytochrome c. These proteins activate caspase-9, triggering the caspase cascade.

2. **Execution:** The caspase cascade is a series of proteolytic enzymes that cleave specific proteins, dismantling the cell. Key caspases involved in leukocyte apoptosis include:
* **Caspase-3:** Cleaves key proteins involved in DNA repair, cytoskeletal integrity, and cell signaling.
* **Caspase-6:** Cleaves nuclear lamins, leading to nuclear fragmentation.
* **Caspase-7:** Cleaves proteins involved in cell adhesion and signaling.

3. **Cell dismantling:** As a result of caspase activity, the leukocyte undergoes characteristic morphological changes:
* **Cell shrinkage:** The cell loses water and becomes smaller.
* **Nuclear fragmentation:** The nucleus condenses and fragments into apoptotic bodies.
* **Plasma membrane blebbing:** The cell membrane forms bulges, eventually shedding apoptotic bodies.
* **Phosphatidylserine exposure:** Phosphatidylserine, normally located on the inner leaflet of the plasma membrane, translocates to the outer leaflet, acting as an "eat me" signal for phagocytes.

4. **Phagocytosis:** Apoptotic bodies are engulfed by phagocytes, such as macrophages, without triggering an inflammatory response. This ensures the removal of cellular debris and prevents the release of potentially harmful intracellular contents.

5. **Regulation:** Apoptotic processes in leukocytes are tightly regulated by complex networks of signaling pathways. Anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, inhibit mitochondrial release of pro-apoptotic proteins, preventing apoptosis. Conversely, pro-apoptotic proteins, such as Bax and Bak, promote mitochondrial release of pro-apoptotic proteins, triggering apoptosis.

6. **Physiological importance:** Leukocyte apoptosis is crucial for maintaining immune homeostasis. It eliminates unwanted or damaged leukocytes, preventing excessive inflammation and autoimmunity. It also plays a key role in resolving infections and preventing chronic inflammation.'
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Proteins (2)

Compounds (30)