Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury

• DOI: 10.1016/j.redox.2024.103469
• Publication Date: 2024-12-12T16:50:23Z
• Authors: Chenxi Zhang; Shujie Zhao; Zhenfei Huang; Ao Xue; Hao Liu; Siming Dai; Ziyang Zheng; Yin Li; Xiaodong Guo; Jun Gu; Feng Zhang; Fubing Wang; Yongxiang Wang; Xiaohua Zhou; Shujun Zhang; Hanwen Zhang; Jun Shen; Jian Chen; Guoyong Yin
• Keywords: Pinocytosis; Foam cell

After spinal cord injury (SCI), phagocytes endocytose myelin debris to form foam cells, exacerbating the inflammatory response. It has been previously shown that macrophages become cells through phagocytosis of via receptor-dependent mechanisms after SCI. Blocking receptor-mediated endocytosis did not completely prevent cell formation, so we investigated receptor-independent endocytosis. Here, revealed formed internalization were predominantly rather than microglia. Receptor-independent macropinocytosis an important position in foamy macrophage formation engagement Mechanistic studies showed cholesterol crystallization following macropinocytosis-mediated promoted reactive oxygen species (ROS) production and NOD-like receptor protein 3 (NLRP3) inflammasome activation, increasing secretion interleukin-1β (IL-1β). Inhibition might reverse this effect, resulting enhanced axonal regeneration reduced neural apoptosis, thereby improving outcomes Overall, our study a unrecognized role for SCI, confer promising therapeutic strategy SCI focus on macropinocytosis.