Antiinflammatory effects of apoptotic cells
Peter M Henson1, Donna L Bratton
1Program in Cell Biology, Department of Pediatrics, National Jewish Health, Denver, Colorado, USA. hensonp@njhealth.org
The Journal of Clinical Investigation
|July 19, 2013
Summary
Phagocytosis of apoptotic cells by macrophages actively suppresses inflammation. This process inhibits inflammatory cytokines and promotes anti-inflammatory factors, aiding tissue repair and immune resolution.
Area of Science:
- Immunology
- Cell Biology
- Inflammation Research
Background:
- Apoptotic cells are cleared by macrophages, a key process in tissue homeostasis.
- This phagocytosis is crucial for immune responses and resolving inflammation.
Purpose of the Study:
- To discuss the relationship between apoptosis, phagocytosis, and inflammation.
- To highlight the anti-inflammatory effects of apoptotic cell clearance.
Main Methods:
- Review of seminal work by Henson, Bratton, and colleagues.
- Discussion of molecular mechanisms underlying inflammation suppression during phagocytosis.
Main Results:
- Phagocytosis of apoptotic cells actively suppresses inflammation.
- Inhibition of pro-inflammatory cytokine production.
- Induction of anti-inflammatory factors like TGF-β and prostaglandin E2.
Conclusions:
- Apoptotic cell phagocytosis is an active anti-inflammatory mechanism.
- This process is critical for tissue remodeling and immune regulation.
- Understanding this interplay is vital for inflammatory disease research.
Related Concept Videos
01:17Phagocytosis 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.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:17The 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...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:31The 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...
01:24Caspases
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.
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...