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Phagocytosis of Apoptotic Cells

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.

Necrosis

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...

The Extrinsic Apoptotic Pathway

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...

Caspases

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

Autophagic Cell Death

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...

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Related Experiment Video

Updated: May 22, 2026

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System

Published on: April 11, 2025

cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting Rip1 and Rip3 activation.

S McComb¹, H H Cheung, R G Korneluk

¹NRC-Institute for Biological Sciences, Ottawa, Ontario, Canada.

Cell Death and Differentiation

|May 12, 2012

Summary

Cellular inhibitor of apoptosis proteins (cIAPs) prevent programmed necrosis in macrophages. Inhibiting cIAPs leads to macrophage death and impairs the immune response to bacterial infections.

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Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

Area of Science:

Immunology
Cell Biology
Molecular Biology

Background:

Cellular inhibitor of apoptosis proteins (cIAPs) are key regulators of cell death, particularly in cancer.
While cIAPs are present in immune tissues, their precise role in immune function is not fully understood.

Purpose of the Study:

To investigate the function of cIAPs in immune cells, specifically macrophages.
To elucidate the mechanism by which cIAPs regulate macrophage cell death and immune response.

Main Methods:

Utilized SMAC mimetics (SM) to induce degradation of cIAPs in primary bone-marrow-derived macrophages.
Assessed macrophage death pathways, including necroptosis, by analyzing TNF receptor expression, Rip1 kinase signaling, and Rip3 knockdown.
Investigated the role of xIAP in SM-induced apoptosis and the impact of cIAPs on Rip1 and Rip3 expression.
Evaluated the in vivo consequences of reduced cIAP activity on macrophage survival and control of Listeria monocytogenes infection.

Main Results:

SM-induced degradation of cIAPs triggered programmed necrosis (necroptosis) in macrophages, dependent on TNF receptor signaling.
Necroptosis was mediated by Rip1 kinase and Rip3, and counteracted by the caspase inhibitor xIAP.
cIAPs were found to limit Rip3 and Rip1 expression post-transcriptionally, inhibiting necrosome formation.
In vivo reduction of cIAP activity led to increased macrophage death and impaired control of Listeria monocytogenes.

Conclusions:

cIAPs play a critical role in suppressing programmed necrosis in macrophages.
This suppression of necroptosis by cIAPs is essential for effective macrophage-mediated control of intracellular bacterial pathogens.