Recommendations from the INHAND Apoptosis/Necrosis Working Group
Susan A Elmore1, Darlene Dixon2, James R Hailey3
1Cellular and Molecular Pathology Branch, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA elmore@niehs.nih.gov.
Toxicologic Pathology
|February 17, 2016
Summary
Toxicologic pathologists should use distinct terms for apoptosis and necrosis when possible. A combined term is recommended when differentiation is uncertain or unnecessary, aiding clear cell death diagnosis.
Area of Science:
- Toxicologic pathology
- Cellular biology
- Histopathology
Background:
- Historically, diagnostic nomenclature for individual cell death, specifically apoptosis and necrosis, has been inconsistent among toxicologic pathologists.
- Recent research highlights distinct cellular pathways for apoptosis and necrosis, crucial for understanding toxicity mechanisms.
Purpose of the Study:
- To provide clear guidance on the nomenclature for distinguishing apoptosis and necrosis in toxicologic pathology.
- To establish diagnostic criteria for common cell death forms based on morphology.
Main Methods:
- Discussion of cellular mechanisms and morphological features of apoptosis and necrosis.
- Development of recommended nomenclature and diagnostic criteria for H&E-stained sections.
- Consideration of special techniques for apoptosis characterization when needed.
Main Results:
- Recommends using 'necrosis' and 'apoptosis' as separate diagnostic terms.
- Advocates for modifiers to describe necrosis distribution (e.g., single cell, focal, diffuse).
- Proposes 'apoptosis/single cell necrosis' when differentiation is not required, possible, or when both are present.
Conclusions:
- Clearer, standardized nomenclature for cell death improves diagnostic accuracy in toxicology.
- Morphological assessment in H&E sections is primary for diagnosis.
- The guidance aims to harmonize nomenclature for the broader toxicologic pathology community.
Related Concept Videos
01:30Apoptosis
16.8K
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...
16.8K
01:31The Intrinsic Apoptotic Pathway
9.1K
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...
9.1K
01:16Necrosis
7.2K
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...
7.2K
01:17The Extrinsic Apoptotic Pathway
9.2K
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...
9.2K
01:30Overview of Cell Death
11.0K
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...
11.0K
01:17Phagocytosis of Apoptotic Cells
5.5K
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...
5.5K