ArticleCell death and differentiation2013
Mouse granzyme A induces a novel death with writhing morphology that is mechanistically distinct from granzyme B-induced apoptosis.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
- Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.Acta neuropathologica · 2026Review
- FOXP3+ T Cells-An Emerging Evidence in Periodontitis Therapeutics.Clinical and experimental dental research · 2025Review
- Hypoxia and IL-15 Cooperate to Induce Perforin Expression by CD8 T Cells and Promote Damage to the Skin in Murine Cutaneous Leishmaniasis.The Journal of investigative dermatology · 2025Article
- Blood-labyrinth barrier damage mediated by granzymes from cytotoxic lymphocytes results in hearing loss in systemic lupus erythematosus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- New Insights on the Potential Role of Pyroptosis in Parkinson's Neuropathology and Therapeutic Targeting of NLRP3 Inflammasome with Recent Advances in Nanoparticle-Based miRNA Therapeutics.Molecular neurobiology · 2025Review
- Single-cell transcriptional responses of T cells during microsporidia infection.Communications biology · 2025Article
- MAIT cells protect against sterile lung injury.Cell reports · 2025Article
- Role of pyroptosis in the pathogenesis of various neurological diseases.Brain, behavior, and immunity · 2024Review
- Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.Cell death & disease · 2024Article
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
- Microarray-based Analysis of Differential Gene Expression Profile in Rotenone-induced Parkinson's Disease Zebrafish Model.CNS & neurological disorders drug targets · 2024Article
- Small Molecule Inhibitors of Lymphocyte Perforin as Focused Immunosuppressants for Infection and Autoimmunity.Journal of medicinal chemistry · 2022Review
- Widespread discrepancy ineLife · 2022Article
- Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia.Cancers · 2022Review
- Opportunities and Challenges in Tunneling Nanotubes Research: How Far from Clinical Application?International journal of molecular sciences · 2021Review
- Article
- Granzyme A inhibition reduces inflammation and increases survival during abdominal sepsis.Theranostics · 2021Article
- Review
- Mechanical, nanomorphological and biological reconstruction of early‑stage apoptosis in HeLa cells induced by cytochalasin B.Oncology reports · 2019Article
- Granzyme A in Chikungunya and Other Arboviral Infections.Frontiers in immunology · 2019Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human and mouse granzyme (Gzm)B both induce target cell apoptosis in concert with pore-forming perforin (Pfp); however the mechanisms by which other Gzms induce non-apoptotic death remain controversial and poorly characterised. We used timelapse microscopy to document, quantitatively and in real time, the death of target cells exposed to primary natural killer (NK) cells from mice deficient in key Gzms. We found that in the vast majority of cases, NK cells from wild-type mice induced classic apoptosis. However, NK cells from syngeneic Gzm B-deficient mice induced a novel form of cell death characterised by slower kinetics and a pronounced, writhing, 'worm-like' morphology. Dying cells initially contracted but did not undergo membrane blebbing, and annexin-V staining was delayed until the onset of secondary necrosis. As it is different from any cell death process previously reported, we tentatively termed this cell death 'athetosis'. Two independent lines of evidence showed this alternate form of death was due to Gzm A: first, cell death was revealed in the absence of Gzm B, but was completely lost when the NK cells were deficient in both Gzm A and B; second, the athetotic morphology was precisely reproduced when recombinant mouse Gzm A was delivered by an otherwise innocuous dose of recombinant Pfp. Gzm A-mediated athetosis did not require caspase activation, early mitochondrial disruption or generation of reactive oxygen species, but did require an intact actin cytoskeleton and was abolished by latrunculin B and mycalolide B. This work defines an authentic role for mouse Gzm A in granule-induced cell death by cytotoxic lymphocytes.
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