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Updated: Jun 1, 2026
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Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis
Published on: November 14, 2025
Lysosomal membrane permeabilization induces cell death in human mast cells
F R Melo1, A Lundequist, G Calounova
1Department of Anatomy, Physiology and Biochemistry, BMC, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Scandinavian Journal of Immunology
|June 8, 2011
Summary
Lysosomotropic agents like Leu-Leu-OMe induce programmed cell death in human mast cells (MC) by destabilizing secretory lysosomes. This targeted apoptosis offers a novel therapeutic strategy for MC-related disorders.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Mast cells (MC) play a pathogenic role in various diseases.
- Stabilizing MC or inducing MC apoptosis are potential therapeutic strategies.
- MC contain secretory lysosomes (granules) with various bioactive compounds.
Purpose of the Study:
- To evaluate if human mast cells undergo cell death upon destabilization of secretory lysosomes.
- To investigate the efficacy of the lysosomotropic agent Leu-Leu-OMe (LLME) in inducing mast cell death.
Main Methods:
- Treatment of human MC, fibroblasts, and HEK-293 cells with LLME.
- Assessment of cell death using Annexin V/propidium iodide staining.
- Measurement of caspase-3-like activity and activated caspase-3 levels.
- Evaluation of cell survival in the presence of caspase inhibitors.
Main Results:
- Human MC exhibited sensitivity to LLME-induced cell death, while fibroblasts and HEK-293 cells were resistant.
- LLME triggered apoptotic cell death, confirmed by caspase-3 activation.
- Cell survival negatively correlated with serglycin expression levels, suggesting its role in LLME-induced death.
Conclusions:
- Secretory lysosome destabilization using lysosomotropic agents is a viable method to induce apoptosis in human mast cells.
- This approach presents a novel therapeutic concept for managing mast cell-mediated diseases.
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