negative regulation of apoptotic cell clearance

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of apoptotic cell clearance. [GOC:obol]

Negative regulation of apoptotic cell clearance is a complex process that involves a precise balance of signaling pathways and cellular mechanisms to ensure efficient and timely removal of dying cells without triggering inflammatory responses. It is crucial for maintaining tissue homeostasis and preventing the development of autoimmune diseases.

The process begins with the recognition of apoptotic cells by phagocytes, such as macrophages and neutrophils. This recognition is mediated by a variety of "eat-me" signals displayed on the surface of apoptotic cells, including phosphatidylserine (PS) exposure, the release of soluble factors like fractalkine and ATP, and the downregulation of "don't eat me" signals.

Once apoptotic cells are recognized, phagocytes engulf them through a process called phagocytosis. This engulfment is tightly regulated and involves the activation of various signaling pathways, including the PI3K/Akt and Rac1 pathways, which promote cytoskeletal rearrangements and membrane remodeling necessary for phagocytosis.

The engulfment process is also influenced by the presence of bridging molecules, such as milk fat globule-EGF factor 8 (MFG-E8) and C1q, which bind to both apoptotic cells and phagocytes, facilitating their interaction.

After engulfment, apoptotic cells are degraded within the phagosome. This degradation is mediated by various lysosomal enzymes and proteases, leading to the breakdown of cellular components into smaller molecules that can be recycled by the phagocyte.

Negative regulation of apoptotic cell clearance involves mechanisms that suppress or fine-tune these processes, ensuring that phagocytosis is not excessive and that the clearance process is controlled.

One crucial aspect of this regulation is the inhibition of "eat-me" signal production and display on the surface of apoptotic cells. This can be achieved through the downregulation of PS exposure, the suppression of soluble factor release, or the upregulation of "don't eat me" signals.

Another important regulatory mechanism is the control of phagocyte activation and engulfment capacity. This can involve the inhibition of signaling pathways that promote phagocytosis, such as the PI3K/Akt and Rac1 pathways, or the downregulation of bridging molecules.

Finally, negative regulation can also occur at the level of phagosome maturation and degradation. This can involve the suppression of lysosomal enzyme activity or the interference with the process of apoptotic cell degradation within the phagosome.

Overall, negative regulation of apoptotic cell clearance is a vital process that ensures the efficient and controlled removal of apoptotic cells, preventing inflammation and maintaining tissue homeostasis.'
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Proteins (1)

Compounds (4)