文献类型：期刊文献

英文题名：Accumulation of Intracellular Ferrous Iron in Inflammatory-Activated Macrophages

作者：Ma, Huijuan[1];Shu, Qi[1];Li, Dan[1];Wang, Tingqian[1];Li, Linyi[1];Song, Xiaodong[2];Lou, Kaiyan[1];Xu, Huan[1]

机构：[1]East China Univ Sci & Technol, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Me, Shanghai Key Lab New Drug Design, State Key Lab Bioreactor Engn,Sch Pharm, Shanghai 200237, Peoples R China;[2]Fudan Univ, Hua Shan Hosp North, Med Lab Dept, Shanghai 201907, Peoples R China

年份：2022

外文期刊名：BIOLOGICAL TRACE ELEMENT RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000827401800001)】；

基金：This work was funded by National Natural Science Foundation of China [grant No. 42177417 to H. X., grant No. 21906057 to H. X., grant No. 21577037 to K. L.]. This work was also funded by Shanghai Science and Technology Committee through Shanghai Sailing Program [grant No. 19YF1412500 to H. X.] and Shanghai Natural Science Fund [grant No. 20ZR1414700 to K. L.]. This work was also funded by Shanghai Municipal Education Commission through the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism [grant No. 2021 Sci & Tech 03-28].

语种：英文

外文关键词：Ferrous iron; Macrophages; Inflammatory activation; Polarization; Ulcerative colitis; Iron metabolism

摘要：Macrophages are important innate immune cells which can be polarized into heterogeneous populations. The inflammatory-activated M1 cells are known to be involved in all kinds of inflammatory diseases, which were also found to be associated with dysregulation of iron metabolism. While iron overload is known to induce M1 polarization, the valence states of iron and its intracellular dynamics during macrophage inflammatory activation have not been identified. In this study, THP-1-derived macrophages were polarized into M1, M2a, M2b, M2c, and M2d cells, and intracellular ferrous iron (Fe(II)) was measured by our previously developed ultrasensitive Fe(II) fluorescent probe. Significant accumulation of Fe(II) was only observed in M1 cells, which was different from the alterations of total iron. Time-dependent change of intracellular Fe(II) during the inflammatory activation was also consistent with the expression shifts of transferrin receptor CD71, ferrireductase Steap3, and Fe(II) exporter Slc40a1. In addition, accumulation of Fe(II) was also found in the colon macrophages of mice with ulcerative colitis, which was positively correlated to inflammatory phenotypes, including the productions of NO, IL-1 beta, TNF-alpha, and IL-6. Collectively, these results demonstrated the specific accumulation of Fe(II) in inflammatory-activated macrophages, which not only enriched our understanding of iron homeostasis in macrophages, but also indicated that Fe(II) could be further developed as a potential biomarker for inflammatory-activated macrophages.