Glossary defining cell death and cell death pathways in relation to procoagulant platelets
| . | Glossary: cell death pathways and procoagulant platelets . |
|---|---|
| Cell death | Defines a process that leads to a point of no return—the termination of the biological function of a cell. |
| Programmed cell death | Cell death under regulated genetic control. |
| Apoptosis | Describes a process of programmed cell death used to dispose of damaged, redundant, or superfluous cells, wherein cells die silently and are removed by macrophages in the absence of inflammatory/reparative responses. |
| Apoptotic cell death pathway | Extrinsic (eg, death receptor initiated) or intrinsic (eg, Bcl-2 family-mediated) biochemical signals result in caspase activation, leading to a series of well-characterized morphological changes (including blebbing, loss of cell membrane asymmetry [PS exposure] and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation), and eventual cell death and clearance. Note: In this article, we have limited our discussion of apoptotic cell death pathways to the intrinsic Bcl-2–mediated pathway implicated in the regulation of platelet lifespan.1 |
| Necrosis | Describes an alternative form of programmed cell death,2-4 often initiated following a chemical (hypoxia, glucose depletion, acidosis), heat-related or mechanical insult. Necrosis results in cell lysis, provoking inflammatory and reparative responses in surrounding cells and tissue. Note: In this article, we refer to cell necrosis, as opposed to tissue necrosis, being the drastic macroscopic tissue changes, visible to the naked eye occurring after cell death.5 |
| Necrotic cell death pathway | Characterized by bioenergetic failure of the cell, followed by loss of plasma membrane integrity, cell and organelle swelling, and cytolysis. These features are a consequence of a defined set of molecular events, including mitochondrial dysfunction (rapid loss of membrane potential, metabolic failure, increased ROS production), sustained toxic intracellular calcium levels and the activation of nonapoptotic proteases such as calpain and lysosomal cathepsins. A key modulator of the necrotic death pathway is the inner mitochondrial membrane protein cyclophilin D (CypD), which controls mitochondrial permeability transition (mPT). |
| Functional necrosis | Certain forms of necrotic cell death are now being reconsidered as normal physiologic programmed cell events. By initiating adaptive responses, necrosis may be considered as an important response to maintain tissue and organism integrity through the initiation of inflammatory and reparative responses.2-4,6-8 |
| Procoagulant platelets | Phosphatidylserine (PS)–positive platelets capable of facilitating thrombin generation. |
| Procoagulant apoptotic platelets | Platelets induced to become procoagulant through a Bak/Bax-mediated apoptotic signaling pathway, in a manner dependent upon caspases but independent of platelet activation and granule release. |
| Procoagulant necrotic platelets | Platelets induced to become procoagulant through potent activation, leading to high sustained levels of cytosolic calcium, rapid mitochondrial dysfunction, and loss of membrane integrity. These platelets are also capable of initiating an inflammatory response. |
| . | Glossary: cell death pathways and procoagulant platelets . |
|---|---|
| Cell death | Defines a process that leads to a point of no return—the termination of the biological function of a cell. |
| Programmed cell death | Cell death under regulated genetic control. |
| Apoptosis | Describes a process of programmed cell death used to dispose of damaged, redundant, or superfluous cells, wherein cells die silently and are removed by macrophages in the absence of inflammatory/reparative responses. |
| Apoptotic cell death pathway | Extrinsic (eg, death receptor initiated) or intrinsic (eg, Bcl-2 family-mediated) biochemical signals result in caspase activation, leading to a series of well-characterized morphological changes (including blebbing, loss of cell membrane asymmetry [PS exposure] and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation), and eventual cell death and clearance. Note: In this article, we have limited our discussion of apoptotic cell death pathways to the intrinsic Bcl-2–mediated pathway implicated in the regulation of platelet lifespan.1 |
| Necrosis | Describes an alternative form of programmed cell death,2-4 often initiated following a chemical (hypoxia, glucose depletion, acidosis), heat-related or mechanical insult. Necrosis results in cell lysis, provoking inflammatory and reparative responses in surrounding cells and tissue. Note: In this article, we refer to cell necrosis, as opposed to tissue necrosis, being the drastic macroscopic tissue changes, visible to the naked eye occurring after cell death.5 |
| Necrotic cell death pathway | Characterized by bioenergetic failure of the cell, followed by loss of plasma membrane integrity, cell and organelle swelling, and cytolysis. These features are a consequence of a defined set of molecular events, including mitochondrial dysfunction (rapid loss of membrane potential, metabolic failure, increased ROS production), sustained toxic intracellular calcium levels and the activation of nonapoptotic proteases such as calpain and lysosomal cathepsins. A key modulator of the necrotic death pathway is the inner mitochondrial membrane protein cyclophilin D (CypD), which controls mitochondrial permeability transition (mPT). |
| Functional necrosis | Certain forms of necrotic cell death are now being reconsidered as normal physiologic programmed cell events. By initiating adaptive responses, necrosis may be considered as an important response to maintain tissue and organism integrity through the initiation of inflammatory and reparative responses.2-4,6-8 |
| Procoagulant platelets | Phosphatidylserine (PS)–positive platelets capable of facilitating thrombin generation. |
| Procoagulant apoptotic platelets | Platelets induced to become procoagulant through a Bak/Bax-mediated apoptotic signaling pathway, in a manner dependent upon caspases but independent of platelet activation and granule release. |
| Procoagulant necrotic platelets | Platelets induced to become procoagulant through potent activation, leading to high sustained levels of cytosolic calcium, rapid mitochondrial dysfunction, and loss of membrane integrity. These platelets are also capable of initiating an inflammatory response. |