Microparticulate Caspase 1 Regulates Gasdermin D and Pulmonary Vascular Endothelial Cell Injury
Srabani Mitra, Matthew Exline, Fabien Habyarimana, Mikhail A Gavrilin, Paul J Baker, Seth L Masters, Mark D Wewers, Anasuya Sarkar
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | AMER THORACIC SOC | Published : 2018
Lung endothelial cell apoptosis and injury occur throughout all stages of acute lung injury/acute respiratory distress syndrome and impact disease progression. Caspases 1, 4, and 5 are essential for completion of the apoptotic program known as pyroptosis that also involves proinflammatory cytokines. Because gasdermin D (GSDMD) mediates pyroptotic death and is essential for pore formation, we hypothesized that it might direct caspase 1-encapsulated microparticle (MP) release and mediate endothelial cell death. Our present work provides evidence that GSDMD is released by LPS-stimulated THP-1 monocytic cells, where it is packaged into microparticles together with active caspase 1. Furthermore, ..View full abstract
Awarded by National Institutes of Health (NIH)
Supported by National Institutes of Health (NIH) grants R01HL24325 (A.S.) and R01GM108928 (A.S. and M.D.W.).