Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury
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 foam cells through the phagocytosis of myelin debris via receptor-dependent mechanisms after SCI. Blocking receptor-med...
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004476 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chenxi Zhang |
| collection | DOAJ |
| description | 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 foam cells through the phagocytosis of myelin debris via receptor-dependent mechanisms after SCI. Blocking receptor-mediated endocytosis did not completely prevent foam cell formation, so we investigated receptor-independent endocytosis. Here, we revealed that foam cells formed after myelin debris internalization were predominantly macrophages rather than microglia. Receptor-independent macropinocytosis has an important position in foamy macrophage formation through engagement of myelin debris endocytosis after SCI. Mechanistic studies showed that cholesterol crystallization following macropinocytosis-mediated foamy macrophage formation promoted the reactive oxygen species (ROS) production and the NOD-like receptor protein 3 (NLRP3) inflammasome activation, increasing the secretion of interleukin-1β (IL-1β). Inhibition of macropinocytosis might reverse this effect, resulting in enhanced axonal regeneration and reduced neural apoptosis, thereby improving outcomes after SCI. Overall, our study revealed a previously unrecognized role for macropinocytosis in foamy macrophages formation after SCI, and confer a promising therapeutic strategy for SCI through focus on macropinocytosis. |
| format | Article |
| id | doaj-art-a038e6ce8a714025af35353c43d978de |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-a038e6ce8a714025af35353c43d978de2025-01-14T04:12:11ZengElsevierRedox Biology2213-23172025-02-0179103469Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injuryChenxi Zhang0Shujie Zhao1Zhenfei Huang2Ao Xue3Hao Liu4Siming Dai5Ziyang Zheng6Yin Li7Xiaodong Guo8Jun Gu9Feng Zhang10Fubing Wang11Yongxiang Wang12Xiaohua Zhou13Shujun Zhang14Hanwen Zhang15Jun Shen16Jian Chen17Guoyong Yin18Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, China; Department of Orthopedics, Suzhou Municipal Hospital, Nanjing Medical University, Jiangsu, Suzhou, 215000, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, Wuhan Union Hospital of China, Huazhong University of Science and Technology, Hubei, Wuhan, 430022, ChinaDepartment of Orthopedics, Xishan People's Hospital of Wuxi City, Southeast University, Jiangsu, Wuxi, 21405, ChinaDepartment of Orthopedics, Xuyi People's Hospital, Yangzhou University, Jiangsu, Xuyi, 211700, ChinaDepartment of Orthopedics, Xuyi People's Hospital, Yangzhou University, Jiangsu, Xuyi, 211700, ChinaDepartment of Orthopedics, Northern Jiangsu People's Hospital, Nanjing Medical University, Jiangsu, Yangzhou, 225001, ChinaDepartment of Anesthesia and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, ChinaDepartment of Orthopedics, Wuxi Ninth Hospital, Suzhou University, Jiangsu, Wuxi, 21405, ChinaDepartment of Pathophysiology, Nanjing Medical University, Jiangsu, Nanjing, 211166, China; Corresponding author.Department of Orthopedics, Suzhou Municipal Hospital, Nanjing Medical University, Jiangsu, Suzhou, 215000, China; Corresponding authors.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, China; Corresponding author.Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Jiangsu, Nanjing, 210029, China; Corresponding authors.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 foam cells through the phagocytosis of myelin debris via receptor-dependent mechanisms after SCI. Blocking receptor-mediated endocytosis did not completely prevent foam cell formation, so we investigated receptor-independent endocytosis. Here, we revealed that foam cells formed after myelin debris internalization were predominantly macrophages rather than microglia. Receptor-independent macropinocytosis has an important position in foamy macrophage formation through engagement of myelin debris endocytosis after SCI. Mechanistic studies showed that cholesterol crystallization following macropinocytosis-mediated foamy macrophage formation promoted the reactive oxygen species (ROS) production and the NOD-like receptor protein 3 (NLRP3) inflammasome activation, increasing the secretion of interleukin-1β (IL-1β). Inhibition of macropinocytosis might reverse this effect, resulting in enhanced axonal regeneration and reduced neural apoptosis, thereby improving outcomes after SCI. Overall, our study revealed a previously unrecognized role for macropinocytosis in foamy macrophages formation after SCI, and confer a promising therapeutic strategy for SCI through focus on macropinocytosis.http://www.sciencedirect.com/science/article/pii/S2213231724004476Spinal cord injuryMacropinocytosisMyelin debrisFoamy macrophageNLRP3 inflammasomeReactive oxygen species |
| spellingShingle | 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 Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury Redox Biology Spinal cord injury Macropinocytosis Myelin debris Foamy macrophage NLRP3 inflammasome Reactive oxygen species |
| title | Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury |
| title_full | Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury |
| title_fullStr | Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury |
| title_full_unstemmed | Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury |
| title_short | Macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate NLRP3 inflammasome after spinal cord injury |
| title_sort | macropinocytosis enhances foamy macrophage formation and cholesterol crystallization to activate nlrp3 inflammasome after spinal cord injury |
| topic | Spinal cord injury Macropinocytosis Myelin debris Foamy macrophage NLRP3 inflammasome Reactive oxygen species |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004476 |
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