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However, the role of MSU crystal physicochemical properties in inducing cell death in neutrophil and macrophage is still unclear. In this study, MSU crystals of different sizes are synthesized to explore the role of pyroptosis in gout. It is demonstrated that MSU crystals induce size\u2010dependent pyroptotic cell death in bone marrow\u2010derived neutrophils (BMNs) and bone marrow\u2010derived macrophages (BMDMs) by triggering NLRP3 inflammasome\u2010dependent caspase\u20101 activation and subsequent formation of N\u2010GSDMD. Furthermore, it is demonstrated that the size of MSU crystal also determines the formation of neutrophil extracellular traps (NETs) and aggregated neutrophil extracellular traps (aggNETs), which are promoted by the addition of interleukin\u20101\u03b2 (IL\u20101\u03b2). Based on these mechanistic understandings, it is shown that N\u2010GSDMD oligomerization inhibitor, dimethyl fumarate (DMF), inhibits MSU crystal\u2010induced pyroptosis in BMNs and J774A.1 cells, and it further alleviates the acute inflammatory response in MSU crystals\u2010induced gout mice model. This study elucidates that MSU crystal\u2010induced pyroptosis in neutrophil and macrophage is critical for the pathological progress of gout, and provides a new therapeutic approach for the treatment of gout.<\/jats:p>","DOI":"10.1002\/smll.202308749","type":"journal-article","created":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T23:52:08Z","timestamp":1704066728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Monosodium Urate Crystal\u2010Induced Pyroptotic Cell Death in Neutrophil and Macrophage Facilitates the Pathological Progress of Gout"],"prefix":"10.1002","volume":"20","author":[{"given":"Chen","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Fine Chemicals Dalian University of Technology  2 Linggong Road Dalian 116024 China"},{"name":"School of Bioengineering Dalian University of Technology  2 Linggong Road Dalian 116024 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