Mouse granzyme A induces a novel death with writhing morphology that is mechanistically distinct from granzyme B-induced apoptosis
O Susanto, SE Stewart, I Voskoboinik, D Brasacchio, M Hagn, S Ellis, S Asquith, KA Sedelies, PI Bird, NJ Waterhouse, JA Trapani
CELL DEATH AND DIFFERENTIATION | NATURE PUBLISHING GROUP | Published : 2013
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 initia..View full abstract
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We thank Dr. Jenny Chia and Dr. Misty Jenkins with assistance in performing additional experiments, Mr. Kevin Thia for assistance in preparation of some of the figures and Dr. Jamie Lopez and Dr. Amelia Brennan for their helpful discussions. OS is supported by a Cancer Research Institute Pre-doctoral Tumour Immunology Scholarship. NJW is supported by a Futures Fellowship from the Australian Research Council (ARC) and the Prostate Cancer Foundation Australia. JAT and PIB are supported by Program and Project grants from the National Health and Medical Research Council (NHMRC), Australia.