engulfment of apoptotic cell

Definition

Target type: biologicalprocess

The removal of the apoptotic cell by phagocytosis, by a neighboring cell or by a phagocyte. [GOC:rk, PMID:15536015]

Engulfment of apoptotic cells is a critical process in multicellular organisms, ensuring the removal of dying cells without triggering inflammation and maintaining tissue homeostasis. This intricate process involves a series of molecular events orchestrated by a complex interplay of signaling pathways, receptors, and effector proteins. Here's a detailed description of the key steps:

**1. Recognition of Apoptotic Cells:**

* **Phosphatidylserine Exposure:** Apoptotic cells undergo significant changes in their cell membrane, with phosphatidylserine (PS) translocating from the inner leaflet to the outer leaflet. This "eat me" signal serves as a beacon for engulfing cells, allowing them to distinguish apoptotic cells from healthy ones.
* **Other "Eat Me" Signals:** Besides PS exposure, apoptotic cells also release other signals, such as calreticulin, thrombospondin, and the chemokine CX3CL1, which further contribute to their recognition.

**2. Binding to Receptors:**

* **Bridging Molecules:** Once apoptotic cells are recognized, engulfing cells utilize bridging molecules, like milk fat globule epidermal growth factor 8 (MFG-E8) and lactadherin, to bind to PS on the apoptotic cell surface. These molecules connect the engulfing cell's receptors to the "eat me" signals.
* **Engulfment Receptors:** Various receptors on the engulfing cell surface, including the tyrosine kinase receptors MerTK, Axl, and Tyro3, as well as the scavenger receptor CD36, bind to these bridging molecules, initiating the engulfment process.

**3. Internalization and Degradation:**

* **Phagocytosis:** Upon receptor activation, the engulfing cell extends pseudopodia, which surround the apoptotic cell and enclose it in a phagosome. This internalization process is driven by cytoskeletal rearrangements and the coordinated action of motor proteins.
* **Phagosome Maturation:** Once internalized, the phagosome undergoes maturation. It fuses with lysosomes, forming a phagolysosome, where the engulfed apoptotic cell is degraded by hydrolytic enzymes. The breakdown products are then recycled or released by the engulfing cell.

**4. Signaling Cascades:**

* **Downstream Signaling:** Receptor engagement triggers downstream signaling cascades, including the activation of PI3K, Akt, and Rac1 pathways, which play crucial roles in regulating cytoskeletal rearrangements and phagosome formation.
* **Anti-Inflammatory Effects:** Engulfment of apoptotic cells also triggers signaling pathways that suppress inflammation, ensuring that the removal of dead cells does not trigger an immune response.

**5. Regulation and Homeostasis:**

* **Fine-Tuned Control:** Engulfment of apoptotic cells is a tightly regulated process, ensuring that only apoptotic cells are removed, while healthy cells remain untouched. The intricate balance of signals and receptors involved in this process ensures proper tissue homeostasis.
* **Immune System Regulation:** The clearance of apoptotic cells by phagocytes is essential for maintaining immune tolerance and preventing autoimmunity. By efficiently removing apoptotic cells, the immune system avoids recognizing them as foreign invaders.

**In Conclusion:**

Engulfment of apoptotic cells is a fundamental biological process that plays a critical role in tissue homeostasis, immune regulation, and the maintenance of cellular integrity. This complex process involves the recognition of apoptotic cells, binding to receptors, internalization, and degradation, all orchestrated by intricate signaling pathways and cellular machinery.'
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Proteins (1)

Compounds (16)