Metabolites released from apoptotic cells act as tissue messengers
Christopher B Medina1,2, Parul Mehrotra3, Sanja Arandjelovic1,2
1Center for Cell Clearance, University of Virginia, Charlottesville, VA, USA.
Nature
|April 3, 2020
Summary
Apoptotic cells actively release specific metabolites, not passively, to signal neighboring cells. This regulated
Area of Science:
- Cell Biology
- Immunology
- Metabolomics
Background:
- Caspase-dependent apoptosis is crucial for tissue homeostasis, regulating inflammation, proliferation, and regeneration.
- The precise mechanisms by which apoptotic cells exert diverse effects on their tissue environment remain incompletely understood.
Purpose of the Study:
- To profile the metabolite secretome of apoptotic cells.
- To investigate the functional impact of these released metabolites on neighboring cells and in disease models.
Main Methods:
- Profiling of the apoptotic metabolite secretome from various cell types.
- Investigating the role of caspase-mediated pannexin 1 channel opening in metabolite release.
- Assessing the effects of apoptotic secretome on gene expression in healthy cells.
- Evaluating the therapeutic potential of apoptotic metabolites in mouse models of inflammatory arthritis and lung-graft rejection.
Main Results:
- Apoptotic cells, while maintaining membrane integrity, release specific, regulated subsets of metabolites.
- Metabolite release is facilitated by caspase-mediated pannexin 1 channel opening, with ongoing metabolic activity.
- The apoptotic secretome suppresses inflammation, cell proliferation, and promotes wound healing in recipient cells.
- A cocktail of apoptotic metabolites significantly reduced disease severity in inflammatory arthritis and lung-graft rejection models.
Conclusions:
- Apoptotic cells actively communicate with their surroundings through a regulated release of metabolites, termed the 'apoptotic secretome'.
- This secretome acts as a 'good-bye' signal, actively modulating tissue responses to promote resolution and homeostasis.
- These findings redefine the role of apoptotic cells from passive entities to active regulators of tissue microenvironments and disease outcomes.
Related Concept Videos
01:17Phagocytosis of Apoptotic Cells
4.8K
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...
Normal cells contain receptors that prevent them from being recognized...
4.8K
01:30Apoptosis
13.6K
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...
13.6K
01:17The Extrinsic Apoptotic Pathway
7.8K
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...
7.8K
01:31The Intrinsic Apoptotic Pathway
8.0K
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...
8.0K
01:30Overview of Cell Death
9.1K
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...
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...
9.1K
01:16Necrosis
6.1K
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...
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...
6.1K